Rak krtani – Patofizjologia i mechanizm

Rak krtani
Patofizjologia i mechanizm

Rak krtani, stanowiący około 33% nowotworów głowy i szyi, to głównie rak płaskonabłonkowy (95-98%), rozwijający się w nadgłośniowej, głośniowej lub podgłośniowej części krtani, z odmiennymi mechanizmami patogenezy i klasyfikacją. Proces onkogenezy obejmuje wieloetapową transformację błony śluzowej od dysplazji do raka inwazyjnego, z kluczową rolą niestabilności chromosomowej i zmian genetycznych, takich jak inaktywacja genów supresorowych p53 (w ~50% przypadków) i p16, amplifikacja cykliny D1 (w ~33%) oraz EGFR (w ~25%). Epigenetyczne modyfikacje, w tym dysregulacja mikroRNA (np. miR-375, miR-205), oraz immunosupresyjne mikrośrodowisko nowotworowe z niskim poziomem nacieku limfocytów T (TILs) wpływają na progresję i rokowanie. Główne czynniki ryzyka to palenie tytoniu (odpowiedzialne za >70% przypadków, zwiększające ryzyko 10-20-krotnie), spożycie alkoholu (szczególnie powyżej 1 drinka dziennie) oraz infekcja HPV (obecna w 11,6-13% przypadków, głównie typ HPV16), choć rola HPV w kancerogenezie raka krtani jest mniej jednoznaczna niż w innych lokalizacjach HNSCC. Dodatkowo, ekspozycja zawodowa na substancje rakotwórcze, zespół metaboliczny oraz czynniki genetyczne i środowiskowe również przyczyniają się do rozwoju choroby.

Patogeneza raka krtani

Rak krtani stanowi około jednej trzeciej wszystkich nowotworów głowy i szyi, będąc istotnym zagrożeniem dla zdrowia publicznego ze względu na wpływ na chorobowość i śmiertelność. Nowotwór ten najczęściej rozwija się w jednej z trzech części krtani – nadgłośniowej, głośniowej lub podgłośniowej – przy czym każda z nich charakteryzuje się własnym systemem klasyfikacji stopnia zaawansowania i specyficznym mechanizmem rozwoju choroby¹. Zrozumienie biologicznych mechanizmów powstawania raka krtani stało się przedmiotem znacznego zainteresowania w ostatnich latach, co pozwoliło na głębsze wniknięcie w złożony proces onkogenezy².

Histopatologia i klasyfikacja

Zdecydowana większość (około 95-98%) nowotworów krtani to raki płaskonabłonkowe (squamous cell carcinoma, SCC), wywodzące się z komórek nabłonka płaskiego wyściełającego wnętrze krtani³⁴. Raki płaskonabłonkowe krtani (LSCC – laryngeal squamous cell carcinoma) różnią się między sobą stopniem zróżnicowania i mogą być klasyfikowane jako dobrze, umiarkowanie lub słabo zróżnicowane⁵. W badaniu mikroskopowym rak krtani charakteryzuje się obecnością komórek wrzecionowatych, bazaloidalnych, atypią jądrową oraz obfitą chromatyną⁶.

W obrazie makroskopowym rak krtani prezentuje się jako spłaszczone blaszki z uniesionymi brzegami oraz owrzodzeniami błony śluzowej⁷. LSCC często rozwija się w środowisku dysplazji nabłonka płaskiego lub raka in situ i typowo prezentuje się jako wyspy, języki i skupiska atypowych komórek naciekających podścielisko krtani⁸.

Wieloetapowy proces kancerogenezy

Rozwój raka krtani to złożony, wieloetapowy proces obejmujący nagromadzenie zmian genetycznych, które prowadzą do transformacji prawidłowej błony śluzowej krtani w tkankę nowotworową⁹. Proces ten postępuje od prawidłowej błony śluzowej krtani do błony śluzowej z dysplazją, następnie do raka in situ, a ostatecznie do raka inwazyjnego¹⁰. Powszechnie przyjmuje się, że rak płaskonabłonkowy wywodzi się z prekursorów przedrakowych, po których następuje rozrost klonalnych komórek z kumulującymi się zmianami genetycznymi i fenotypowymi, prowadzącymi do inwazyjnego nowotworu złośliwego¹¹.

Kluczowym elementem patogenezy raka krtani jest niestabilność chromosomowa w zmianach prekursorowych, która wiąże się ze znacznie zwiększonym ryzykiem progresji do raka inwazyjnego¹². Proces transformacji nowotworowej obejmuje liczne zmiany genetyczne, w tym inaktywację genów supresorowych nowotworów i aktywację proto-onkogenów poprzez delecje, mutacje punktowe, metylację promotorów i amplifikację genów¹³.

Kluczowe alteracje genetyczne

Badania zidentyfikowały szereg genów odgrywających kluczową rolę w patogenezie raka krtani. Należą do nich:¹⁴¹⁵¹⁶:

p53 (TP53) – inaktywacja tego genu supresorowego występuje w około 50% przypadków raka krtani
p16 (CDKN2a/INK4a) – inaktywacja występuje w około 50% przypadków, niezależnie od infekcji HPV
Cyklina D1 (CCND1) – amplifikacja występuje w około jednej trzeciej przypadków, związana z zaawansowanymi stadiami
EGFR (receptor naskórkowego czynnika wzrostu) – amplifikacja dotyczy około jednej czwartej przypadków
NOTCH1 – zaburzenia ekspresji
Inne geny: p14 (ARF), FHIT, RASSF1A, RB1

We wczesnym etapie procesu nowotworowego zmieniona funkcja genu p53 i nadekspresja genu CCND1 zwiększają niestabilność genetyczną i promują dalsze zmiany genetyczne i chromosomalne. Amplifikacja CCND1 jest uważana za ostateczne zdarzenie transformujące poprzez selekcję złośliwego subklonu z genetycznie zmienionego pola¹⁷. Receptor EGFR jest często i wcześnie nadekspresjonowany w LSCC, głównie poprzez mechanizmy potranslacyjne¹⁸.

W raku krtani obserwuje się znacznie wyższy wskaźnik mutacji związanych z paleniem tytoniu w porównaniu do innych raków płaskonabłonkowych głowy i szyi¹⁹. Zmiany w ekspresji białka p53 i mutacje genu p53 zostały zaproponowane jako niezależne czynniki predykcyjne nawrotu w LSCC, jednak ich wartość prognostyczna jest kontrowersyjna²⁰.

MikroRNA i mechanizmy epigenetyczne

Według najnowszych dowodów, modyfikacje epigenetyczne przyczyniają się do rozwoju raka krtani. W szczególności długie niekodujące RNA (lncRNA), mikroRNA (miRNA) i mRNA odgrywają istotną rolę w rozwoju nowotworów, wpływając na różnicowanie, proliferację i apoptozę komórek nowotworowych²¹.

MikroRNA (miR) to klasa małych niekodujących RNA, które potranskrypcyjnie regulują ekspresję genów. Zaburzona ekspresja mikroRNA jest często obserwowana u pacjentów z rakiem krtani. Liczne badania wykazały, że mikroRNA odgrywają znaczącą rolę w patogenezie raka krtani poprzez regulację proliferacji komórek nowotworowych, przerzutów, inwazji i apoptozy²².

Niektóre mikroRNA są wyciszane epigenetycznie przez hipermetylację DNA. Wśród mikroRNA w raku krtani, zmiana w miR-137 obejmuje nieprawidłową hipermetylację²³. Wcześniejsze badania wykazały, że miR-375 i miR-205 były znacząco dysregulowane w raku płaskonabłonkowym krtani, co przyczyniało się do inwazji i migracji LSCC. Wyniki wykazały, że miR-375 i miR-205 synergistycznie regulują inwazję i migrację LSCC za pośrednictwem szlaku AKT-zależnej przemiany nabłonkowo-mezenchymalnej (EMT)²⁴.

Rola mikrośrodowiska nowotworu

Mikrośrodowisko nowotworowe w raku krtani odzwierciedla dynamiczną interakcję między komórkami nowotworowymi, komponentami stromalnymi i elementami układu odpornościowego. Przewlekły stan zapalny i ekspozycja na toksyny środowiskowe tworzą immunosupresyjne środowisko, zdominowane przez regulatorowe limfocyty T i komórki supresyjne pochodzenia szpikowego²⁵.

Badania wykazały, że naciek limfocytów (TILs) oraz ekspresja genów związanych z aktywacją układu odpornościowego (FCGR1A, IFNA17, FCRLA, NCR3, KREMEN1, CD14, CD3G, CD19, CD20 i CD79A) są znacząco związane z czynnikami prognostycznymi lub przeżyciem swoistym dla choroby²⁶. Niski poziom TILs był silnie związany z nawrotem w ciągu 2 lat. Hipoteza badaczy sugeruje, że zmieniona aktywacja odpowiedzi immunologicznej prowadzi do nieskutecznego blokowania wzrostu guza, sprzyjając w ten sposób zjawiskom ucieczki guza i wystąpieniu lokalnego nawrotu²⁷.

W zaawansowanym raku krtani podkreślono i potwierdzono rolę TILs jako niezależnego czynnika prognostycznego. Jakość i ilość TILs determinuje odpowiedź przeciwnowotworową, będąc bezpośrednio związaną z prognozą pacjentów i czasem przeżycia wolnym od choroby²⁸.

Czynniki ryzyka i ich wpływ na patogenezę

Palenie tytoniu i spożycie alkoholu

Palenie tytoniu jest najważniejszym czynnikiem ryzyka rozwoju raka krtani, odpowiadającym za ponad 70% wszystkich przypadków²⁹³⁰. Osoby palące papierosy mają 10-20 razy wyższe ryzyko rozwoju raka krtani w porównaniu z osobami niepalącymi³¹. Palący, którzy zostali zdiagnozowani z rakiem krtani, są również narażeni na ryzyko nowotworów w pozostałej części dróg pokarmowo-oddechowych³².

Wydaje się, że nikotyna sama w sobie nie jest odpowiedzialna za rozwój raka, ale rakotwórcze działanie wykazują wielopierścieniowe węglowodory aromatyczne i nitrozoaminy obecne w dymie tytoniowym³³. Ryzyko maleje gwałtownie po zaprzestaniu palenia, chociaż nigdy nie osiąga poziomu osób, które nigdy nie paliły³⁴.

Spożycie alkoholu jest również istotnym czynnikiem ryzyka, choć jego niezależny wpływ jest trudny do określenia ze względu na częste współwystępowanie z paleniem tytoniu³⁵. Spożywanie alkoholu, szczególnie w dużych ilościach (więcej niż jeden drink dziennie), zwiększa ryzyko rozwoju raka krtani. Co istotne, jednoczesne używanie alkoholu i tytoniu ma efekt mnożnikowy, znacznie zwiększając ryzyko³⁶³⁷.

Mechanizm kancerogenezy związany z alkoholem nie jest w pełni zrozumiany. Uważa się, że jest związany z trwałym uszkodzeniem nici DNA przez metabolit alkoholu zwany aldehydem octowym. Inne sugerowane mechanizmy obejmują niedobory żywieniowe i warianty genetyczne³⁸.

Infekcja HPV

W ostatnich latach coraz większą uwagę zwraca się na rolę zakażenia wirusem brodawczaka ludzkiego (HPV) w rozwoju raka krtani. HPV, szczególnie typy wysokiego ryzyka, takie jak HPV16, został zidentyfikowany jako kluczowy czynnik patogenny, zwłaszcza u młodszej populacji i pacjentek płci żeńskiej³⁹.

Infekcja HPV może wpływać na rozwój i progresję raka krtani na trzech poziomach: DNA, mRNA i białka⁴⁰. Integracja DNA wirusa HPV może prowadzić do mutacji genetycznych i zaburzeń ekspresji w komórkach gospodarza, co prowadzi do zaburzeń metabolicznych komórek i złośliwej proliferacji⁴¹.

Najważniejszym mechanizmem kancerogenezy związanym z HPV jest nadmierna ekspresja białek E6 i E7 wirusa HPV o wysokim ryzyku (HR-HPV). Gdy HR-HPV16 i 18 zakażają krtań, produkt genu wczesnego – białko E6 – może wiązać się z białkiem p53, tworząc kompleks powodujący inaktywację p53, a tym samym uniemożliwiając rolę białka p53 w hamowaniu nowotworu w komórkach⁴².

Ekspresja mRNA HR-HPV odgrywa ważną rolę w rozwoju i progresji raka krtani. Występowanie i rozwój raka krtani są ściśle związane z nadekspresją białka HPV16 E7 i cykliny D1⁴³.

Należy jednak zauważyć, że w przeciwieństwie do raka płaskonabłonkowego gardła środkowego, rola HPV w kancerogenezie raka płaskonabłonkowego krtani nie została jednoznacznie ustalona⁴⁴. HPV występuje w mniejszości przypadków raka krtani, przy czym najnowsze badania wykazują, że około 11,6% i 13% przypadków jest pozytywnych dla HPV⁴⁵.

Ekspozycja zawodowa i środowiskowa

Długotrwała ekspozycja zawodowa na określone substancje rakotwórcze może zwiększać ryzyko rozwoju raka krtani. Do substancji tych należą nikiel, gaz musztardowy oraz opary kwasu siarkowego⁴⁶. Inne substancje potencjalnie rakotwórcze obejmują formaldehyd, chlorek winylu i benzopireny⁴⁷.

Ekspozycja na azbest, pył drzewny, pył cementowy, produkty smołowe, skórę i metale również wiąże się z podwyższonym ryzykiem⁴⁸. Ponadto, długotrwała ekspozycja na bierne palenie tytoniu zwiększa ryzyko raka krtani⁴⁹.

Zespół metaboliczny i refluks żołądkowo-przełykowy

Zespół metaboliczny (MetS) został zidentyfikowany jako niezależny czynnik ryzyka rozwoju raka krtani. Badania wykazały, że częstość występowania raka krtani w grupie z MetS była znacząco wyższa niż w grupie bez MetS, niezależnie od wieku, płci, statusu palenia, spożycia alkoholu i wysiłku fizycznego⁵⁰.

Istnieje silny związek między liczbą składników MetS a wskaźnikiem ryzyka raka krtani. Spośród trzech składników MetS, kombinacja podwyższonej glukozy na czczo, podwyższonych trójglicerydów i niskiego HDL była związana z najwyższym ryzykiem raka krtani⁵¹.

Możliwe mechanizmy kancerogenezy związane z MetS obejmują⁵²:

Insulinooporność i hiperinsulinemię
Przewlekły subkliniczny stan zapalny
Nieprawidłowości w metabolizmie hormonów płciowych
Uszkodzenia spowodowane ekspozycją na substancje zaburzające funkcjonowanie układu hormonalnego i zanieczyszczenie powietrza
Przewlekłą hiperglikemię
Zaburzenia zegara okołodobowego

Hiperinsulinemia, insulinooporność i hiperglikemia zwiększają proliferację, angiogenezę, uszkodzenie cząsteczki DNA przez aktywne formy tlenu z powodu nadmiaru glukozy, ruchliwość komórkową i apoptozę⁵³.

Jeśli chodzi o refluks żołądkowo-przełykowy (GERD), jego rola w patogenezie raka krtani jest kontrowersyjna. Niektóre badania sugerują, że refluks jest czynnikiem ryzyka dla raka krtani i gardła⁵⁴. „Cichy refluks”, kiedy kwas żołądkowy przepływa w górę przełyku i rozlewa się na krtań, jest czynnikiem drażniącym, który zmywa śluz pełniący funkcję ochronną. Na przykład, jeśli palisz, śluz chroni przed dotarciem substancji rakotwórczych do błony śluzowej, ale jeśli refluks zmywa tę ochronę, zwiększa to ryzyko rozwoju raka⁵⁵. Jednak inne badania nie potwierdziły hipotezy, że refluks żołądkowo-przełykowy i krtaniowo-gardłowy są czynnikami rakotwórczymi dla błony śluzowej krtaniowo-gardłowej⁵⁶.

Inne czynniki ryzyka

Do innych potencjalnych czynników ryzyka rozwoju raka krtani należą⁵⁷⁵⁸⁵⁹:

Infekcje wirusem opryszczki pospolitej
Nadmierne obciążanie głosu
Przewlekłe zapalenie krtani
Niedobory żywieniowe (np. ryboflawiny)
Dieta bogata w czerwone mięso, żywność przetworzoną i smażoną
Zespół Plummera-Vinsona
Wdychanie pary wodnej i gorąca
Oparzenia termiczne
Ekspozycja na promieniowanie jonizujące
Predyspozycje rodzinne

Czynniki genetyczne mogą również odgrywać rolę w rozwoju raka krtani. Osoby z niedokrwistością Fanconiego, która jest stanem powodującym problemy z krwią od młodego wieku, oraz dyskeratozą wrodzoną, która jest zespołem wpływającym na skórę, paznokcie i krew, mogą być bardziej narażone na rozwój wielu typów raka głowy i szyi⁶⁰.

Mechanizmy rozprzestrzeniania się nowotworu

Wzorce rozprzestrzeniania się raka krtani zależą od lokalizacji guza pierwotnego i charakterystycznego unaczynienia limfatycznego w danej lokalizacji⁶¹⁶². Raki krtani są kategoryzowane na nadgłośniowe, głośniowe i podgłośniowe, przy czym patofizjologia i leczenie różnią się dla każdej z tych podlokalizacji⁶³.

Rak nadgłośniowy

Rak nadgłośniowy rozwija się w strukturach położonych powyżej głośni, obejmujących nagłośnię, fałdy nalewkowo-nagłośniowe, fałdy przedsionkowe (fałszywe struny głosowe), a także głęboką przestrzeń przed nagłośniową i paraspłośniową⁶⁴.

Wczesne zajęcie układu limfatycznego jest charakterystyczną cechą raków nadgłośniowych, przy czym 55% pacjentów wykazuje kliniczne dowody przerzutów do węzłów chłonnych w momencie rozpoznania⁶⁵. Ta wysoka skłonność do przerzutów wynika z bogatego obustronnego unaczynienia limfatycznego nadgłośni, która rozwija się z linii pośrodkowej zawiązka buccofaryngealnego z łuków skrzelowych 4 i 6⁶⁶.

Rak nadgłośniowy może przez długi czas nie powodować znaczących objawów, aż do momentu gdy osiągnie stosunkowo duży rozmiar, kiedy to niedrożność dróg oddechowych może być pierwszym objawem⁶⁷.

Rak głośniowy

Rak głośniowy rozwija się z prawdziwych strun głosowych⁶⁸. W przeciwieństwie do raka nadgłośniowego, rak głośniowy objawia się wcześnie poprzez zmiany jakości głosu, dlatego często jest wykrywany we wczesnym stadium⁶⁹.

Głośnia, w przeciwieństwie do struktur nadgłośniowych, powstaje z linii pośrodkowej fuzji struktur bocznych pochodzących z zawiązka tchawiczo-oskrzelowego z łuków 4, 5 i 6 i charakteryzuje się względnym brakiem naczyń limfatycznych⁷⁰. W konsekwencji, ta granica embriologiczna ogranicza rozprzestrzenianie się podśluzówkowe do sąsiednich miejsc w krtani we wczesnym stadium nowotworu, a brak naczyń limfatycznych w głośni ogranicza rozprzestrzenianie się limfatyczne do szyi, pozwalając rakom głośniowym pozostać zlokalizowanymi w krtani przez dłuższy czas⁷¹.

Guzy głośniowe nie stanowią ryzyka zajęcia układu limfatycznego, chyba że występuje rozrost nadgłośniowy lub głośniowy⁷². Dzięki temu raki głośniowe mają najlepsze rokowanie wśród nowotworów krtani⁷³.

Rak podgłośniowy

Rak podgłośniowy rozwija się poniżej prawdziwych strun głosowych, w obszarze od 5 mm poniżej wolnego brzegu struny głosowej do dolnej krawędzi chrząstki pierścieniowatej⁷⁴. Jest to najrzadszy typ raka krtani, stanowiący zaledwie 1-8% wszystkich pierwotnych nowotworów krtani⁷⁵.

Rak podgłośniowy wywołuje minimalne objawy, co odpowiada za jego późne rozpoznanie, które w połączeniu z wczesnymi przerzutami do węzłów chłonnych oznacza złe rokowanie⁷⁶. Ten typ nowotworu krtani ma największą tendencję do rozprzestrzeniania się do innych części ciała we wczesnych stadiach⁷⁷.

Wzorce inwazji i przerzutów

Z wyjątkiem nowotworów w zaawansowanym stadium, większość raków krtani ma tendencję do pozostawania ograniczonymi do jednego miejsca anatomicznego ze względu na mechanizm wzrostu guza polegający na wypychaniu tkanek⁷⁸. Ponadto, struktury chrzęstne i powięziowe, takie jak chrząstki tarczowata i pierścieniowata z pokrywającym je ochrzęstną, kieszonka krtaniowa, stożek sprężysty, błony czworokątna i tarczowo-gnykowa oraz więzadło gnykowe-nagłośniowe, działają jako bariery dla rozprzestrzeniania się⁷⁹.

Spoidło przednie i błona tarczowo-gnykowa, w przeciwieństwie do powyższych struktur, oferują niewielki opór dla rozprzestrzeniania się guza⁸⁰. Obecność nacieku gardłowego, potwierdzonego patologicznie dodatniego stadium 2-3, bliskich lub mikroskopowo dodatnich marginesów oraz inwazji naczyń limfatycznych i okołonerwowej mają negatywny wpływ na rokowanie⁸¹.

Rak krtani, który rozprzestrzenia się poza krtań, może naciekać tarczycę, tchawicę, przełyk, język, płuca, wątrobę i kości⁸². Przerzuty odległe występują najczęściej w płucach i wątrobie⁸³.

Nowe strategie terapeutyczne oparte na mechanizmach patogenezy

Zrozumienie mechanizmów patogenezy raka krtani doprowadziło do rozwoju nowych strategii terapeutycznych, które celują w specyficzne szlaki molekularne zaangażowane w progresję nowotworową.

Immunoterapia

Inhibitory punktów kontrolnych immunologicznych (ICIs) zrewolucjonizowały onkologię, przeciwdziałając indukowanej przez nowotwór ucieczce immunologicznej, przywracając nadzór immunologiczny i aktywując odpowiedzi limfocytów T przeciwko rakowi⁸⁴. ICIs działają poprzez blokowanie cząsteczek punktów kontrolnych, takich jak PD-1 (programmed cell death-1), PD-L1 (programmed death-ligand 1) i CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), które nowotwory wykorzystują do uniknięcia wykrycia przez układ odpornościowy⁸⁵.

Zatwierdzenie ICIs, a mianowicie nivolumabu i pembrolizumabu, do leczenia raka krtani zostało poparte próbami klinicznymi wykazującymi ich skuteczność w zaawansowanym raku płaskonabłonkowym głowy i szyi (HNSCC)⁸⁶. Integracja ICIs z ustalonymi metodami leczenia ma zrewolucjonizować leczenie raka krtani, zmierzając w kierunku terapii skoncentrowanej na pacjencie⁸⁷.

Terapia genowa i molekularna

Podejście do terapii genowej p53 już wykazało indukowanie apoptozy, radio- i chemosensytyzację w liniach komórkowych, a to, w połączeniu z radioterapią lub chemioterapią, jest racjonalną możliwością⁸⁸. Funkcjonalna klasyfikacja mutantów p53 oparta na EAp53 może przewidzieć specyficzny dla choroby wskaźnik przeżycia z zaawansowanym rakiem krtani i mutacją p53⁸⁹.

Badania na poziomie komórkowym wykazały, że miR-548-3p reguluje zawartość białka DAG1, a następnie dodatkowo indukuje złośliwą transformację raka krtani⁹⁰. Bezpośrednie działanie DAG1 z białkami LAMA2 i UTRN wzmacnia zdolność komórek raka krtani do proliferacji, migracji i inwazji, tym samym zwiększając złośliwość raka krtani we wszystkich kierunkach⁹¹.

Badania wykazały, że circ-RANBP9 hamuje proliferację, inwazję i migrację komórek raka krtani⁹². Wyniki wskazują, że circ-RANBP9 hamuje przerzuty raka krtani⁹³.

Terapia celowana

Terapia celowana to rodzaj leczenia, który wykorzystuje leki lub inne substancje do identyfikacji i atakowania określonych komórek nowotworowych⁹⁴. Leki te celują w komórki nowotworowe z określonymi typami białek, zapobiegając namnażaniu się komórek⁹⁵.

Radiosensybilizatory to leki, które sprawiają, że komórki guza stają się bardziej wrażliwe na radioterapię. Połączenie radioterapii z radiosensybilizatorami może zabić więcej komórek guza⁹⁶.

Badania nad nowymi typami leczenia obejmują chemoprofilaktykę, która polega na stosowaniu leków, witamin lub innych substancji w celu zmniejszenia ryzyka rozwoju raka lub zmniejszenia ryzyka nawrotu raka⁹⁷.

Podsumowanie

Rak krtani to złożona choroba, której patogeneza obejmuje wieloetapowy proces kumulacji zmian genetycznych i epigenetycznych, prowadzących do transformacji prawidłowej błony śluzowej krtani w tkankę nowotworową. Najważniejszymi czynnikami ryzyka są palenie tytoniu i spożycie alkoholu, które działają synergistycznie, zwiększając ryzyko rozwoju nowotworu. Inne czynniki, takie jak infekcja HPV, ekspozycja zawodowa i środowiskowa, zespół metaboliczny oraz predyspozycje genetyczne, również odgrywają rolę w patogenezie raka krtani.

Zrozumienie molekularnych mechanizmów rozwoju raka krtani doprowadziło do opracowania nowych strategii terapeutycznych, w tym immunoterapii, terapii genowej i molekularnej oraz terapii celowanej. Te innowacyjne podejścia, w połączeniu z tradycyjnymi metodami leczenia, takimi jak chirurgia, radioterapia i chemioterapia, oferują nadzieję na poprawę wyników leczenia pacjentów z rakiem krtani.

Dalsze badania nad patogenezą raka krtani są niezbędne do pełnego zrozumienia złożonych interakcji między czynnikami genetycznymi, epigenetycznymi, środowiskowymi i immunologicznymi, które przyczyniają się do rozwoju i progresji tego nowotworu. Takie badania mogą prowadzić do opracowania bardziej skutecznych metod profilaktyki, wczesnego wykrywania i leczenia raka krtani, ostatecznie poprawiając rokowanie pacjentów cierpiących na tę chorobę.

Kolejne rozdziały

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Wybierz kolejny rozdział z menu poniżej, aby otworzyć nową podstronę kompedium wiedzy i uzyskać szczegółowe informację o leku, substancji lub chorobie.

Materiały źródłowe

#1 Laryngeal Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK526076/
Laryngeal cancer accounts for one-third of head and neck cancers, posing a significant global health concern due to its impact on morbidity and mortality. […] This activity reviews the prevalence, incidence, associated risk factors, and underlying disease pathophysiology of laryngeal cancer, as well as thoroughly discusses the clinical presentation, diagnostic modalities, and available treatment options. […] Laryngeal cancers represent one-third of all head and neck cancers and are a significant source of morbidity and mortality. These cancers primarily originate from any of the 3 subdivisions of the larynxâthe supraglottis, glottis, and subglottisâand each maintains its own staging system. […] Laryngeal cancers are most often diagnosed in patients with a significant smoking history, who are also at risk for cancers in the remainder of the aerodigestive tract.
#2 Updates on Larynx Cancer: Risk Factors and Oncogenesis
https://www.mdpi.com/1422-0067/24/16/12913
Laryngeal cancer is a very common tumor in the upper aero-digestive tract. Understanding its biological mechanisms has garnered significant interest in recent years. The development of laryngeal squamous cell carcinoma (LSCC) follows a multistep process starting from precursor lesions in the epithelium. […] Cancer development involves multiple steps, and genetic alterations play a crucial role. Tumor suppressor genes can be inactivated, and proto-oncogenes may become activated through mechanisms like deletions, point mutations, promoter methylation, and gene amplification. […] According to the latest evidence, epigenetic modifications have been proven to contribute to LSCC development. Particularly, lncRNAs, miRNAs, and mRNAs play a relevant role in cancer development, including differentiation, proliferation, and apoptosis of cancer cells.
#3 Laryngeal Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK526076/
Smoking is the most significant risk factor for laryngeal cancer, accounting for over 70% of all cases. […] Other risk factors for laryngeal cancer include long-term secondhand smoke exposure, male sex, white or black race, genetic and other syndromes, and occupational and environmental exposures. […] The vast majority of laryngeal cancers are squamous cell carcinomas. […] Patterns of spread depend on the location of the primary tumor and the inherent lymphatic supply at that location. Laryngeal cancers are categorized into supraglottic, glottic, and subglottic subsites, with pathophysiology and treatment differing for each subsite. […] Each primary subsite of laryngeal carcinoma carries different implications in symptomatic presentation, patterns of spread, prognosis, and treatment paradigms. […] Early-stage disease is often highly treatable or curable in the supraglottis and glottis, although the prognosis remains poor in the subglottis.
#4 Squamous cell carcinoma of the larynx | Radiology Reference Article | Radiopaedia.org
https://radiopaedia.org/articles/squamous-cell-carcinoma-of-the-larynx?lang=us
Squamous cell carcinoma (SCC) accounts for 98% of laryngeal tumors. […] SCC arises from the epiglottis, aryepiglottic fold, false vocal fold, as well as the deep pre-epiglottic and paraglottic space. It metastasizes early to cervical lymph nodes. […] SCC arises from the true vocal fold. It manifests early due to hoarseness of voice and rarely metastasizes due to the poor lymphatic drainage of the glottis. […] SCC arises from anywhere below the true vocal fold to the inferior edge of the cricoid cartilage. It produces minimal symptoms, which is responsible for its late diagnosis, which coupled with early lymph node metastasis, means a poor prognosis.
#5 Head and Neck: Laryngeal tumors: an overview
https://atlasgeneticsoncology.org/solid-tumor/5087/head-and-neck-laryngeal-tumors-an-overview
The vast majority of all laryngeal malignancies (95%) are conventional squamous cell carcinomas (SCC) and they vary according to their degree of differentiation to well, moderate and poor carcinomas. […] SCC often arises in a background of mucosal squamous dysplasia or carcinoma in situ and typically presents islands, tongues and clusters of atypical cells invading the laryngeal stroma. […] Early in the cancerous process altered p53 gene function and CCND1 gene overexpression increase genetic instability and promote further genetic and chromosomal alterations, such as CCND1 amplification which is considered as the ultimate transforming event by the selection of a malignant subclone from a genetically altered field. […] EGFR is frequently and early overexpressed in LSCC, mainly by post-translational mechanisms.
#6 Laryngeal cancer pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Laryngeal_cancer_pathophysiology
Laryngeal cancer arises from squamous cells, which are cells that are normally involved in protection of upper respiratory airway. Genes involved in the pathogenesis of laryngeal cancer include p16, NOTCH1, cyclin D1, and TP53. […] Development of laryngeal cancer is the result of multiple genetic mutations. These mutations lead to activation of oncogenes and inactivation of tumor suppression genes which ultimately result in deregulated cellular proliferation. Genes involved in the pathogenesis of laryngeal cancer include: […] On gross pathology, laryngeal cancer is characterized by: Flattened plaques, Raised margins of the lesion, Mucosal ulceration. […] On microscopic histopathological analysis, laryngeal carcinoma is characterized by: Spindle cells, Basaloid cells, Nuclear atypia, Abundant chromatin.
#7 Laryngeal cancer pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Laryngeal_cancer_pathophysiology
Laryngeal cancer arises from squamous cells, which are cells that are normally involved in protection of upper respiratory airway. Genes involved in the pathogenesis of laryngeal cancer include p16, NOTCH1, cyclin D1, and TP53. […] Development of laryngeal cancer is the result of multiple genetic mutations. These mutations lead to activation of oncogenes and inactivation of tumor suppression genes which ultimately result in deregulated cellular proliferation. Genes involved in the pathogenesis of laryngeal cancer include: […] On gross pathology, laryngeal cancer is characterized by: Flattened plaques, Raised margins of the lesion, Mucosal ulceration. […] On microscopic histopathological analysis, laryngeal carcinoma is characterized by: Spindle cells, Basaloid cells, Nuclear atypia, Abundant chromatin.
#8 Head and Neck: Laryngeal tumors: an overview
https://atlasgeneticsoncology.org/solid-tumor/5087/head-and-neck-laryngeal-tumors-an-overview
The vast majority of all laryngeal malignancies (95%) are conventional squamous cell carcinomas (SCC) and they vary according to their degree of differentiation to well, moderate and poor carcinomas. […] SCC often arises in a background of mucosal squamous dysplasia or carcinoma in situ and typically presents islands, tongues and clusters of atypical cells invading the laryngeal stroma. […] Early in the cancerous process altered p53 gene function and CCND1 gene overexpression increase genetic instability and promote further genetic and chromosomal alterations, such as CCND1 amplification which is considered as the ultimate transforming event by the selection of a malignant subclone from a genetically altered field. […] EGFR is frequently and early overexpressed in LSCC, mainly by post-translational mechanisms.
#9 Malignant Tumors of the Larynx: Practice Essentials, History Of The Procedure, Problem
https://emedicine.medscape.com/article/848592-overview
Malignant tumors of the larynx may affect laryngeal physiology depending on tumor location and size. Supraglottic tumors may not alter laryngeal function until they reach a relatively large size, at which time airway obstruction may be the first symptom. Conversely, glottic tumors alter voice quality early in their development and are thus often discovered at an early stage. […] Development and progression of malignant tumors of the larynx occurs at the molecular and histologic level. The molecular steps involved in tumorigenesis have not been fully elucidated and likely vary from patient to patient. Histologic progression occurs from normal laryngeal mucosa to dysplastic mucosa to carcinoma in situ to invasive carcinoma. This progression is a multistep process of accumulated genetic events that lead to the development of larynx tumors.
#10 Malignant Tumors of the Larynx: Practice Essentials, History Of The Procedure, Problem
https://emedicine.medscape.com/article/848592-overview
Malignant tumors of the larynx may affect laryngeal physiology depending on tumor location and size. Supraglottic tumors may not alter laryngeal function until they reach a relatively large size, at which time airway obstruction may be the first symptom. Conversely, glottic tumors alter voice quality early in their development and are thus often discovered at an early stage. […] Development and progression of malignant tumors of the larynx occurs at the molecular and histologic level. The molecular steps involved in tumorigenesis have not been fully elucidated and likely vary from patient to patient. Histologic progression occurs from normal laryngeal mucosa to dysplastic mucosa to carcinoma in situ to invasive carcinoma. This progression is a multistep process of accumulated genetic events that lead to the development of larynx tumors.
#11 Updates on Larynx Cancer: Risk Factors and Oncogenesis
https://www.mdpi.com/1422-0067/24/16/12913
It is widely assumed that SCC arises from a premalignant progenitor, followed by the outgrowth of clonal cells with cumulative genetic alterations and phenotypic changes that lead to invasive malignancy. […] For all cancer variants, frequent genetic alterations occur, such as inactivation of tumor suppressor genes and activation of proto-oncogenes through deletions, point mutations, promoter methylation, and gene amplification. […] The transformation of laryngeal normal mucosa in SCC is a multi-step process, and the microbiome seems to play an active role in this process. […] The intricate interplay between lncRNAs, miRNAs, and mRNAs holds promising insights improved strategies for the diagnosis, treatment, and prognosis of LSCC.
#12 Pathology Outlines – Squamous cell carcinoma of larynx
https://www.pathologyoutlines.com/topic/larynxscc.html
Malignant proliferation of squamous epithelial cells […] Most common primary cancer of the larynx (CA Cancer J Clin 2017;67:31) […] Strong association with smoking and alcohol use […] Chromosomal instability in precursor lesions has been associated with a significantly increased rate of progression to invasive cancer (Pathology 2014;46:216) […] Several driver gene mutations have been implicated in oncogenesis, including p53, cyclin D1, p16 (CDKN2a / INK4a, independent of human papillomavirus [HPV]), p14 (ARF), FHIT, RASSF1A, EGFR and RB1 (J Clin Pathol 2006;59:445, N Engl J Med 2007;357:2552) […] Significantly higher rate of smoking related mutations in laryngeal SCC compared to other head and neck SCCs (Sci Rep 2019;9:19256) […] Smoking is strongly associated with laryngeal SCC development (Eur Arch Otorhinolaryngol 2017;274:1617)
#13 Updates on Larynx Cancer: Risk Factors and Oncogenesis
https://www.mdpi.com/1422-0067/24/16/12913
It is widely assumed that SCC arises from a premalignant progenitor, followed by the outgrowth of clonal cells with cumulative genetic alterations and phenotypic changes that lead to invasive malignancy. […] For all cancer variants, frequent genetic alterations occur, such as inactivation of tumor suppressor genes and activation of proto-oncogenes through deletions, point mutations, promoter methylation, and gene amplification. […] The transformation of laryngeal normal mucosa in SCC is a multi-step process, and the microbiome seems to play an active role in this process. […] The intricate interplay between lncRNAs, miRNAs, and mRNAs holds promising insights improved strategies for the diagnosis, treatment, and prognosis of LSCC.
#14 Laryngeal cancer pathophysiology – wikidoc
https://www.wikidoc.org/index.php/Laryngeal_cancer_pathophysiology
Laryngeal cancer arises from squamous cells, which are cells that are normally involved in protection of upper respiratory airway. Genes involved in the pathogenesis of laryngeal cancer include p16, NOTCH1, cyclin D1, and TP53. […] Development of laryngeal cancer is the result of multiple genetic mutations. These mutations lead to activation of oncogenes and inactivation of tumor suppression genes which ultimately result in deregulated cellular proliferation. Genes involved in the pathogenesis of laryngeal cancer include: […] On gross pathology, laryngeal cancer is characterized by: Flattened plaques, Raised margins of the lesion, Mucosal ulceration. […] On microscopic histopathological analysis, laryngeal carcinoma is characterized by: Spindle cells, Basaloid cells, Nuclear atypia, Abundant chromatin.
#15 Pathology Outlines – Squamous cell carcinoma of larynx
https://www.pathologyoutlines.com/topic/larynxscc.html
Malignant proliferation of squamous epithelial cells […] Most common primary cancer of the larynx (CA Cancer J Clin 2017;67:31) […] Strong association with smoking and alcohol use […] Chromosomal instability in precursor lesions has been associated with a significantly increased rate of progression to invasive cancer (Pathology 2014;46:216) […] Several driver gene mutations have been implicated in oncogenesis, including p53, cyclin D1, p16 (CDKN2a / INK4a, independent of human papillomavirus [HPV]), p14 (ARF), FHIT, RASSF1A, EGFR and RB1 (J Clin Pathol 2006;59:445, N Engl J Med 2007;357:2552) […] Significantly higher rate of smoking related mutations in laryngeal SCC compared to other head and neck SCCs (Sci Rep 2019;9:19256) […] Smoking is strongly associated with laryngeal SCC development (Eur Arch Otorhinolaryngol 2017;274:1617)
#16 KEGG DISEASE: Laryngeal cancer
https://www.genome.jp/dbget-bin/www_bget?ds:H00055
Laryngeal cancer is one of the most common malignancies in Europe, with about 52,000 new cases per year, 90% of them occurring in men. […] Some molecular events have been described in laryngeal squamous cell carcinoma (LSCC). Although tumor suppressor inactivation of p53 and p16 is common in these tumors (about 50% each), oncogenic activation is less well characterized. Cyclin D1 and epidermal growth factor receptor amplification have been reported in one-third and one-quarter of LSCCs, respectively, both related to advanced stages, whereas c-myc could be amplified in 13% of cases although without associated overexpression.
#17 Head and Neck: Laryngeal tumors: an overview
https://atlasgeneticsoncology.org/solid-tumor/5087/head-and-neck-laryngeal-tumors-an-overview
The vast majority of all laryngeal malignancies (95%) are conventional squamous cell carcinomas (SCC) and they vary according to their degree of differentiation to well, moderate and poor carcinomas. […] SCC often arises in a background of mucosal squamous dysplasia or carcinoma in situ and typically presents islands, tongues and clusters of atypical cells invading the laryngeal stroma. […] Early in the cancerous process altered p53 gene function and CCND1 gene overexpression increase genetic instability and promote further genetic and chromosomal alterations, such as CCND1 amplification which is considered as the ultimate transforming event by the selection of a malignant subclone from a genetically altered field. […] EGFR is frequently and early overexpressed in LSCC, mainly by post-translational mechanisms.
#18 Head and Neck: Laryngeal tumors: an overview
https://atlasgeneticsoncology.org/solid-tumor/5087/head-and-neck-laryngeal-tumors-an-overview
The vast majority of all laryngeal malignancies (95%) are conventional squamous cell carcinomas (SCC) and they vary according to their degree of differentiation to well, moderate and poor carcinomas. […] SCC often arises in a background of mucosal squamous dysplasia or carcinoma in situ and typically presents islands, tongues and clusters of atypical cells invading the laryngeal stroma. […] Early in the cancerous process altered p53 gene function and CCND1 gene overexpression increase genetic instability and promote further genetic and chromosomal alterations, such as CCND1 amplification which is considered as the ultimate transforming event by the selection of a malignant subclone from a genetically altered field. […] EGFR is frequently and early overexpressed in LSCC, mainly by post-translational mechanisms.
#19 Pathology Outlines – Squamous cell carcinoma of larynx
https://www.pathologyoutlines.com/topic/larynxscc.html
Malignant proliferation of squamous epithelial cells […] Most common primary cancer of the larynx (CA Cancer J Clin 2017;67:31) […] Strong association with smoking and alcohol use […] Chromosomal instability in precursor lesions has been associated with a significantly increased rate of progression to invasive cancer (Pathology 2014;46:216) […] Several driver gene mutations have been implicated in oncogenesis, including p53, cyclin D1, p16 (CDKN2a / INK4a, independent of human papillomavirus [HPV]), p14 (ARF), FHIT, RASSF1A, EGFR and RB1 (J Clin Pathol 2006;59:445, N Engl J Med 2007;357:2552) […] Significantly higher rate of smoking related mutations in laryngeal SCC compared to other head and neck SCCs (Sci Rep 2019;9:19256) […] Smoking is strongly associated with laryngeal SCC development (Eur Arch Otorhinolaryngol 2017;274:1617)
#20 Head and Neck: Laryngeal tumors: an overview
https://atlasgeneticsoncology.org/solid-tumor/5087/head-and-neck-laryngeal-tumors-an-overview
Alterations of p53 protein expression and mutations of the p53 gene have been proposed as independent predictors of recurrence in LSCC, however with controversial prognostic value. […] In LSCC, degradation mediated by other cellular proteins, such as MDM2 or by human papillomavirus (HPV) E6 oncoprotein may represent alternative pathways leading to loss of p53 function. […] A p53 gene therapy approach has already been shown to induce apoptosis, radio- and chemosensitisation in cell lines and this, in combination with radiotherapy or chemotherapy, is a rational possibility.
#21 Updates on Larynx Cancer: Risk Factors and Oncogenesis
https://www.mdpi.com/1422-0067/24/16/12913
Laryngeal cancer is a very common tumor in the upper aero-digestive tract. Understanding its biological mechanisms has garnered significant interest in recent years. The development of laryngeal squamous cell carcinoma (LSCC) follows a multistep process starting from precursor lesions in the epithelium. […] Cancer development involves multiple steps, and genetic alterations play a crucial role. Tumor suppressor genes can be inactivated, and proto-oncogenes may become activated through mechanisms like deletions, point mutations, promoter methylation, and gene amplification. […] According to the latest evidence, epigenetic modifications have been proven to contribute to LSCC development. Particularly, lncRNAs, miRNAs, and mRNAs play a relevant role in cancer development, including differentiation, proliferation, and apoptosis of cancer cells.
#22 The role of MicroRNAs expression in laryngeal cancer | Oncotarget
https://www.oncotarget.com/article/4195/text/
MicroRNAs (miRs, miRs) is a class of small non-coding RNAs, which posttranscriptionally regulate gene expression. Deregulated miRs are frequently observed in patients with laryngeal cancer. In addition, numerous studies have showed miRs play significant roles in the pathogenesis of laryngeal cancer through regulating tumor cell proliferation, metastasis, invasion and apoptosis. […] The recently discovered microRNAs (miRs or miRs) have been implicated in the development of laryngeal cancer. […] miRs play significant roles in the pathogenesis of cancers, acting as oncogenes, tumor suppressors, or modulators of cancer stem cells. […] Dysregulation of Dicer or other enzymes in the miR biogenesis is hypothesized to be a common feature in tumors. […] Expression of Dicer was higher in the LSCC, significantly correlated with the pTNM stage and tumor lymph node metastasis.
#23 The role of MicroRNAs expression in laryngeal cancer | Oncotarget
https://www.oncotarget.com/article/4195/text/
Some miRs are silenced epigenetically by DNA hypermethylation. Among miRs in laryngeal cancer, the change in miR-137 involves aberrant hypermethylation. […] It is clear that miRs play significant roles in the pathogenesis of laryngeal cancer. Functional analyses of miRs may contribute to clinical applications in the near future.
#24 Cancer of the Larynx | CancerIndex
http://www.cancerindex.org/clinks2y.htm
Laryngeal cancer is a malignancy arising in the tissues of the larynx (voicebox). […] Most laryngeal cancers are of squamous cell histology, these can be categorised as either keratinizing or non-keratinizing. […] Previous studies have found that miR-375 and miR-205 were significantly dysregulated in laryngeal squamous cell carcinoma, which contributed to the invasion and migration of LSCC. […] Our results showed that miR-375 and miR-205 regulated the invasion and migration of LSCC via AKT-mediated EMT synergistically. […] The study found that vascular endothelial growth factor overexpression predicted a worse prognosis for laryngeal cancer patients. […] CCR6 is the receptor of CCL20 chemokine, but its function in laryngeal cancer is not known. […] RUNX3, an important tumor suppressor, is known to relate to lymph node metastasis and the development of LSCC.
#25 Releasing the brakes: the role of immune checkpoint inhibitors in laryngeal cancer
https://www.explorationpub.com/Journals/etat/Article/1002292
The tumor microenvironment in laryngeal cancer reflects a dynamic interplay among tumor cells, stromal components, and immune elements. Chronic inflammation and exposure to environmental toxins create an immunosuppressive milieu, dominated by regulatory T-cells and myeloid-derived suppressor cells. […] The incorporation of ICIs into laryngeal cancer treatment represents a transformative step, offering new opportunities for personalized therapeutic strategies. […] The exploration of ICIs in the treatment of laryngeal cancer has gained significant momentum through numerous clinical trials, reflecting the growing interest in harnessing the potential of immunotherapy. […] These trials aim to assess the efficacy, safety, and role of ICIs in overcoming the limitations of conventional therapies.
#26 A role for the immune system in advanced laryngeal cancer | Scientific Reports
https://www.nature.com/articles/s41598-020-73747-0
To investigate the role of the altered activation of the immune system in the prognosis of patients affected by laryngeal squamous cell carcinoma (LSCC). […] TILs and the expression of genes related with immune system activation (FCGR1A, IFNA17, FCRLA, NCR3, KREMEN1, CD14, CD3G, CD19, CD20 and CD79A) were significantly associated with prognostic factors or disease specific survival. […] Low TILs count was highly associated with relapse within 2 years (p0.001). […] Low TILs and altered expression of specific genes associated with tumor-immune systems interactions emerged as independent risk factors, associated to poor prognosis and relapse within 2 years in advanced LSCC. […] Our hypothesis is that an altered immune response activation leads to an ineffective tumor growth block, thus favoring the tumor escape phenomena and local relapse presentation.
#27 A role for the immune system in advanced laryngeal cancer | Scientific Reports
https://www.nature.com/articles/s41598-020-73747-0
To investigate the role of the altered activation of the immune system in the prognosis of patients affected by laryngeal squamous cell carcinoma (LSCC). […] TILs and the expression of genes related with immune system activation (FCGR1A, IFNA17, FCRLA, NCR3, KREMEN1, CD14, CD3G, CD19, CD20 and CD79A) were significantly associated with prognostic factors or disease specific survival. […] Low TILs count was highly associated with relapse within 2 years (p0.001). […] Low TILs and altered expression of specific genes associated with tumor-immune systems interactions emerged as independent risk factors, associated to poor prognosis and relapse within 2 years in advanced LSCC. […] Our hypothesis is that an altered immune response activation leads to an ineffective tumor growth block, thus favoring the tumor escape phenomena and local relapse presentation.
#28 A role for the immune system in advanced laryngeal cancer | Scientific Reports
https://www.nature.com/articles/s41598-020-73747-0
In advanced LSCC we highlighted and confirmed the role of TILs as an independent prognostic factor. […] The quality and quantity of TILs determines the antitumor response, being directly related with patients prognosis and DFS. […] Our data suggest a significant correlation between high-level of TILs which enrich the tumor-host interface and both B-cell lineage (CD20 and CD19) and T-cell lineage (CD3G and CD8). […] Moreover, by multivariate analyses, adjusting for all known prognostic factors and tumor characteristics, of the 19 down regulated genes emerged with OIRRA, only three (FCGR1A, FCRLA and IFNA17) were identified as independent risk factors for DFS. […] The expression of FCRLA was recently discovered in human immature plasmacytoid dendritic cells (pDCs), indicating that FCRLA could perhaps participate in chaperone-mediated protein folding both in pDCs and B cells.
#29 Laryngeal Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK526076/
Smoking is the most significant risk factor for laryngeal cancer, accounting for over 70% of all cases. […] Other risk factors for laryngeal cancer include long-term secondhand smoke exposure, male sex, white or black race, genetic and other syndromes, and occupational and environmental exposures. […] The vast majority of laryngeal cancers are squamous cell carcinomas. […] Patterns of spread depend on the location of the primary tumor and the inherent lymphatic supply at that location. Laryngeal cancers are categorized into supraglottic, glottic, and subglottic subsites, with pathophysiology and treatment differing for each subsite. […] Each primary subsite of laryngeal carcinoma carries different implications in symptomatic presentation, patterns of spread, prognosis, and treatment paradigms. […] Early-stage disease is often highly treatable or curable in the supraglottis and glottis, although the prognosis remains poor in the subglottis.
#30 Laryngeal Cancer | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/24035
Smoking is the most significant risk factor for laryngeal cancer, accounting for over 70% of all cases. […] Heavy alcohol consumption is also a risk factor, though its independent effect is unclear due to its frequent combination with tobacco use. […] Other risk factors for laryngeal cancer include long-term secondhand smoke exposure, male sex, white or black race, genetic and other syndromes, and occupational and environmental exposures. […] The vast majority of laryngeal cancers are squamous cell carcinomas. […] Patterns of spread depend on the location of the primary tumor and the inherent lymphatic supply at that location. […] Laryngeal cancers are categorized into supraglottic, glottic, and subglottic subsites, with pathophysiology and treatment differing for each subsite. […] Early lymphatic involvement is a hallmark of supraglottic cancers, with 55% of patients showing clinical evidence of nodal metastasis at presentation.
#31 Laryngeal Cancer: Diagnosis and Preoperative Work-up | Ento Key
https://entokey.com/laryngeal-cancer-diagnosis-and-preoperative-work-up/
Except for advance stage tumors, most laryngeal cancers tend to remain confined to one anatomic site because of the pushing mechanism of tumor growth. […] Additionally, cartilaginous and fascial anatomic structures, such as the thyroid and cricoid cartilages with their overlying perichondrium, the ventricle, the conus elasticus, the quadrangular and thyrohyoid membranes, and the hyoepiglottic ligament, act as barriers to spread. […] The anterior commisure and thyrohyoid membrane, in contradistinction to the above structures, offers little resistance to tumor spread. […] Eighty-five percent of laryngeal cancers can be attributed to tobacco and alcohol use. Smoking is the predominant risk factor for laryngeal carcinoma with alcohol use being an independent and synergistic risk factor. […] Current smokers have a 10- to 20-fold increased risk of laryngeal cancer compared with nonsmokers.
#32 Laryngeal Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK526076/
Laryngeal cancer accounts for one-third of head and neck cancers, posing a significant global health concern due to its impact on morbidity and mortality. […] This activity reviews the prevalence, incidence, associated risk factors, and underlying disease pathophysiology of laryngeal cancer, as well as thoroughly discusses the clinical presentation, diagnostic modalities, and available treatment options. […] Laryngeal cancers represent one-third of all head and neck cancers and are a significant source of morbidity and mortality. These cancers primarily originate from any of the 3 subdivisions of the larynxâthe supraglottis, glottis, and subglottisâand each maintains its own staging system. […] Laryngeal cancers are most often diagnosed in patients with a significant smoking history, who are also at risk for cancers in the remainder of the aerodigestive tract.
#33 Head and Neck: Laryngeal tumors: an overview
https://atlasgeneticsoncology.org/solid-tumor/5087/head-and-neck-laryngeal-tumors-an-overview
More than 95% of laryngeal tumours are squamous cell carcinomas (SCC). […] The exact cause of laryngeal cancer is still unknown. However, several interrelated co-factors (mainly tobacco smoking and alcohol consumption), are clearly associated with an increased incidence in laryngeal cancer. […] It appears that nicotine is not responsible for cancer itself, but polycyclic aromatic hydrocarbons and nitrosamines are carcinogenic. […] Infections from herpes simplex and HPV, gastroesophageal reflex disease, anatomical malformations, Plummer-Vinson syndrome, steam and heat inhalation, thermal burns and exposure to ionizing radiation, asbestos, nickel, textile fibers and various chemicals, like formaldehyde, vinyl chloride and benzopyrenes, have also been considered as aetiological factors.
#34 Laryngeal Cancer: Diagnosis and Preoperative Work-up | Ento Key
https://entokey.com/laryngeal-cancer-diagnosis-and-preoperative-work-up/
However, these risks decline sharply after smoking cessation although never to the same level as patients who have never smoked. […] While smoking cessation is the single most effective means of preventing laryngeal cancer, it is equally important to encourage patients to quit smoking after the diagnosis of laryngeal cancer has been made. […] Smoking has been identified as an independent risk factor for local recurrence and for recurrence at an earlier time point than those who ceased smoking. […] Additionally, there is a controversial association with chronic gastroesophageal reflux as well as an increased incidence of squamous cell carcinoma in preexisting laryngeal respiratory papillomatosis.
#35 Laryngeal Cancer | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/24035
Smoking is the most significant risk factor for laryngeal cancer, accounting for over 70% of all cases. […] Heavy alcohol consumption is also a risk factor, though its independent effect is unclear due to its frequent combination with tobacco use. […] Other risk factors for laryngeal cancer include long-term secondhand smoke exposure, male sex, white or black race, genetic and other syndromes, and occupational and environmental exposures. […] The vast majority of laryngeal cancers are squamous cell carcinomas. […] Patterns of spread depend on the location of the primary tumor and the inherent lymphatic supply at that location. […] Laryngeal cancers are categorized into supraglottic, glottic, and subglottic subsites, with pathophysiology and treatment differing for each subsite. […] Early lymphatic involvement is a hallmark of supraglottic cancers, with 55% of patients showing clinical evidence of nodal metastasis at presentation.
#36 Laryngeal Cancer: Symptoms, Causes & Treatment
https://my.clevelandclinic.org/health/diseases/16611-laryngeal-cancer
Cancer affecting your larynx or vocal cords happens when cells grow uncontrollably in your larynx. As these cancerous (malignant) cells multiply, they invade tissues and damage your body. […] Some forms of HPV (human papillomavirus), a sexually transmitted infection (STI), can cause laryngeal cancer. […] You also have a much higher chance of developing it if you use tobacco or drink alcohol frequently. […] Smoking or using other tobacco products greatly increases your risk of developing laryngeal cancer. Drinking alcohol, especially a lot of it (more than one drink daily) also raises your risk. And using alcohol and tobacco together increases your risk even more. […] Laryngeal cancer that spreads beyond your larynx may invade your thyroid, windpipe (trachea), esophagus, tongue, lungs, liver and bones.
#37 Pathology Outlines – Squamous cell carcinoma of larynx
https://www.pathologyoutlines.com/topic/larynxscc.html
Heavy alcohol use is an established risk factor […] Combined smoking and alcohol use have a multiplicative effect on risk […] HPV is found in a minority of cases, with recent studies finding 11.6% and 13% of cases positive (J Pathol Transl Med 2020;54:411, Oral Oncol 2019;98:20) […] Unlike oropharyngeal SCC, the role of HPV in the carcinogenesis of laryngeal SCC has not been established (Head Neck 2011;33:581, Nat Rev Dis Primers 2020;6:92) […] Epithelial dysplasia is accepted as a precursor lesion
#38 Head and neck cancer – Wikipedia
https://en.wikipedia.org/wiki/Head_and_neck_cancer
Laryngeal cancer begins in the larynx, or „voice box”, and is the second most common type of head and neck cancer encountered. Cancer may occur on the vocal folds themselves („glottic” cancer) or on tissues above and below the true cords („supraglottic” and „subglottic” cancers, respectively). Laryngeal cancer is strongly associated with tobacco smoking. […] Alcohol and tobacco use are major risk factors for head and neck cancer. 72% of head and neck cancer cases are caused by using both alcohol and tobacco. This rises to 89% when looking specifically at laryngeal cancer. […] The way in which alcohol contributes to cancer development is not fully understood. It is thought to be related to permanent damage of DNA strands by a metabolite of alcohol called acetaldehyde. Other suggested mechanisms include nutritional deficiencies and genetic variations.
#39 Global, regional, and national mortality of larynx cancer from 1990 to 2021: results from the global burden of disease study | World Journal of Surgical Oncology | Full Text
https://wjso.biomedcentral.com/articles/10.1186/s12957-025-03720-6
Larynx cancer, a major upper respiratory tract malignancy, remains a global public health challenge, driven by smoking, alcohol use, and chronic inflammation, despite medical and public health advancements. […] In recent years, increasing attention has been given to the role of HPV infection in the development of larynx cancer. HPV, particularly high-risk types such as HPV16, has been identified as a key pathogenic factor, especially in younger populations and female patients, with its pathogenic role becoming more evident. […] Emerging research highlights the role of HPV infection in larynx cancer pathogenesis, particularly in younger populations and female patients. High-risk HPV subtypes, such as HPV16, are increasingly recognized as key etiological factors, shifting the understanding of larynx cancer from traditional risk factors alone to a more complex interplay of viral and environmental factors.
#40 Effect of HPV Infection on the Occurrence and Development of Laryngeal Cancer: A Review
https://www.jcancer.org/v10p4455.htm
Laryngeal cancer has the second highest incidence of head and neck malignant tumors worldwide. […] In recent years, studies have shown that human papillomavirus (HPV) infection may be a high-risk factor for laryngeal cancer and closely related to the development and prognosis of laryngeal cancer. […] The mechanism of the occurrence and development of laryngeal cancer caused by HPV infection needs investigation, as does a rapid and effective HPV detection method for effectively preventing the occurrence of laryngeal cancer and controlling its development. […] The possible mechanism of HPV infection affecting the development and progression of laryngeal cancer is described at the following three levels: DNA, mRNA and protein. […] HPV infection mainly affects the occurrence and development of laryngeal cancer by integrating in the host cell genome, activating the expression of proto-oncogenes and inhibiting the expression of tumor suppressor genes.
#41 Effect of HPV Infection on the Occurrence and Development of Laryngeal Cancer: A Review
https://www.jcancer.org/v10p4455.htm
The integration of the HPV DNA can lead to genetic mutation and expression disorder of host cells, which leads to cell metabolic disorder and malignant proliferation. […] When HPV infects the larynx, it can promote the development of laryngeal cancer by activating the expression of various proto-oncogenes. […] HPV infection causes laryngeal cancer, which is also associated with tumor suppressor gene mutation and inactivation. […] HPV infection can also be carcinogenic by interacting with the apoptotic inhibiting gene, survivin, cyclin D1 and human telomere reverse transcriptase, thus accelerating cell cycle progression, inhibiting cell senescence, and promoting tumorigenesis. […] The mRNA expression of HPV can indicate that tumor transformation is caused by HPV, although this postulation does not exclude that other carcinogens may also play a role in the carcinogenic effect.
#42 Effect of HPV Infection on the Occurrence and Development of Laryngeal Cancer: A Review
https://www.jcancer.org/v10p4455.htm
The mRNA expression of HR-HPV plays an important role in the development and progression of laryngeal cancer. […] HPV infection induces laryngeal cancer mainly because of excessive expression of HR-HPV E6 and E7 proteins. […] The occurrence and development of laryngeal cancer is closely related to the overexpression of HPV16 E7 protein and cyclin D1. […] Studies have shown that after HR-HPV16 and 18 infect the larynx, the early gene product E6 protein can bind with p53 protein and form a complex resulting in p53 inactivation and thus hindering the role of p53 protein in tumor inhibition in cells. […] The functional classification of p53 mutants based on EAp53 can predict the disease-specific survival rate with advanced laryngeal cancer and p53 mutation. […] The expression of p16 protein is slightly lower in laryngeal carcinoma than benign laryngeal lesions and significantly lower than in vocal polyps. […] Therefore, we must deeply study the molecular mechanism of laryngeal cancer caused by HPV infection.
#43 Effect of HPV Infection on the Occurrence and Development of Laryngeal Cancer: A Review
https://www.jcancer.org/v10p4455.htm
The mRNA expression of HR-HPV plays an important role in the development and progression of laryngeal cancer. […] HPV infection induces laryngeal cancer mainly because of excessive expression of HR-HPV E6 and E7 proteins. […] The occurrence and development of laryngeal cancer is closely related to the overexpression of HPV16 E7 protein and cyclin D1. […] Studies have shown that after HR-HPV16 and 18 infect the larynx, the early gene product E6 protein can bind with p53 protein and form a complex resulting in p53 inactivation and thus hindering the role of p53 protein in tumor inhibition in cells. […] The functional classification of p53 mutants based on EAp53 can predict the disease-specific survival rate with advanced laryngeal cancer and p53 mutation. […] The expression of p16 protein is slightly lower in laryngeal carcinoma than benign laryngeal lesions and significantly lower than in vocal polyps. […] Therefore, we must deeply study the molecular mechanism of laryngeal cancer caused by HPV infection.
#44 Pathology Outlines – Squamous cell carcinoma of larynx
https://www.pathologyoutlines.com/topic/larynxscc.html
Heavy alcohol use is an established risk factor […] Combined smoking and alcohol use have a multiplicative effect on risk […] HPV is found in a minority of cases, with recent studies finding 11.6% and 13% of cases positive (J Pathol Transl Med 2020;54:411, Oral Oncol 2019;98:20) […] Unlike oropharyngeal SCC, the role of HPV in the carcinogenesis of laryngeal SCC has not been established (Head Neck 2011;33:581, Nat Rev Dis Primers 2020;6:92) […] Epithelial dysplasia is accepted as a precursor lesion
#45 Pathology Outlines – Squamous cell carcinoma of larynx
https://www.pathologyoutlines.com/topic/larynxscc.html
Heavy alcohol use is an established risk factor […] Combined smoking and alcohol use have a multiplicative effect on risk […] HPV is found in a minority of cases, with recent studies finding 11.6% and 13% of cases positive (J Pathol Transl Med 2020;54:411, Oral Oncol 2019;98:20) […] Unlike oropharyngeal SCC, the role of HPV in the carcinogenesis of laryngeal SCC has not been established (Head Neck 2011;33:581, Nat Rev Dis Primers 2020;6:92) […] Epithelial dysplasia is accepted as a precursor lesion
#46 Laryngeal cancer | EBSCO Research Starters
https://www.ebsco.com/research-starters/health-and-medicine/laryngeal-cancer
Laryngeal cancer can form in any part of the larynx, although 60 percent of cases start in the glottis. […] Almost all cancers of the larynx start in the squamous cells that line its inner walls, and these cancers are known as squamous cell carcinomas. […] A link has been detected between laryngeal cancer and long-term occupational exposure to particular carcinogens, notably nickel, mustard gas, and fumes from sulfuric acid. […] The major risk factors for laryngeal cancer are tobacco use and moderate or heavy alcohol consumption. […] The cancer can spread (metastasize) to the lymph nodes in the neck, the back of the tongue, and other parts of the throat and neck. […] Cancers that develop below the vocal cords are particularly problematic because the vocal cords can prevent these cancers from being seen.
#47 Head and Neck: Laryngeal tumors: an overview
https://atlasgeneticsoncology.org/solid-tumor/5087/head-and-neck-laryngeal-tumors-an-overview
More than 95% of laryngeal tumours are squamous cell carcinomas (SCC). […] The exact cause of laryngeal cancer is still unknown. However, several interrelated co-factors (mainly tobacco smoking and alcohol consumption), are clearly associated with an increased incidence in laryngeal cancer. […] It appears that nicotine is not responsible for cancer itself, but polycyclic aromatic hydrocarbons and nitrosamines are carcinogenic. […] Infections from herpes simplex and HPV, gastroesophageal reflex disease, anatomical malformations, Plummer-Vinson syndrome, steam and heat inhalation, thermal burns and exposure to ionizing radiation, asbestos, nickel, textile fibers and various chemicals, like formaldehyde, vinyl chloride and benzopyrenes, have also been considered as aetiological factors.
#48 Cancer of larynx | PPT
https://www.slideshare.net/AnilKumarGowda/cancer-of-larynx-67119139
Cancer of the larynx is a malignant tumor of the voice box that is most commonly squamous cell carcinoma. It occurs more frequently in men ages 50-70 who smoke or drink alcohol. […] Carcinogenes that have been associated with laryngeal cancer include tobacco (smoke or smokeless and alcohol and their combined effects, as well as exposure to asbestos, mustard gas, wood dust, cement dust, tar products, leather, and metals. Other contributing factors include straining the voice, chronic laryngitis, nutritional deficiency (riboflavin) and family predispostions. […] Treatment of laryngeal cancers depends on the staging of the tumor, which includes location, size, and histology of the tumor and the presence and extent of cervical lymph node involvement. Treatment options include Surgery Radiation therapy and Chemotherapy.
#49 Laryngeal Cancer | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/24035
Smoking is the most significant risk factor for laryngeal cancer, accounting for over 70% of all cases. […] Heavy alcohol consumption is also a risk factor, though its independent effect is unclear due to its frequent combination with tobacco use. […] Other risk factors for laryngeal cancer include long-term secondhand smoke exposure, male sex, white or black race, genetic and other syndromes, and occupational and environmental exposures. […] The vast majority of laryngeal cancers are squamous cell carcinomas. […] Patterns of spread depend on the location of the primary tumor and the inherent lymphatic supply at that location. […] Laryngeal cancers are categorized into supraglottic, glottic, and subglottic subsites, with pathophysiology and treatment differing for each subsite. […] Early lymphatic involvement is a hallmark of supraglottic cancers, with 55% of patients showing clinical evidence of nodal metastasis at presentation.
#50 Metabolic Syndrome and Incidence of Laryngeal Cancer: A Nationwide Cohort Study | Scientific Reports
https://www.nature.com/articles/s41598-018-37061-0
It is unknown whether the presence of metabolic syndrome (MetS) affects the incidence of laryngeal cancer. […] Age, gender, smoking status, alcohol intake, and exercise-adjusted hazard ratios indicated that participants with MetS had a 1.13-fold higher hazard of having larynx cancer than those without MetS. […] MetS was found to be an independent risk factor for the incidence of laryngeal cancer. In Korea, MetS and its components are significantly associated with the development of laryngeal cancer. […] From the result of our present study, we proved that the prevalence of laryngeal cancer among a group with MetS was significantly higher than that among a group without MetS independent of age, gender, smoking status, alcohol intake, and exercise. […] A strong association has been found between the number of MetS components and the HR of laryngeal cancer. Of the three MetS components, the combination of elevated FBG, elevated TG, and low HDL was related to the highest risk of laryngeal cancer.
#51 Metabolic Syndrome and Incidence of Laryngeal Cancer: A Nationwide Cohort Study | Scientific Reports
https://www.nature.com/articles/s41598-018-37061-0
It is unknown whether the presence of metabolic syndrome (MetS) affects the incidence of laryngeal cancer. […] Age, gender, smoking status, alcohol intake, and exercise-adjusted hazard ratios indicated that participants with MetS had a 1.13-fold higher hazard of having larynx cancer than those without MetS. […] MetS was found to be an independent risk factor for the incidence of laryngeal cancer. In Korea, MetS and its components are significantly associated with the development of laryngeal cancer. […] From the result of our present study, we proved that the prevalence of laryngeal cancer among a group with MetS was significantly higher than that among a group without MetS independent of age, gender, smoking status, alcohol intake, and exercise. […] A strong association has been found between the number of MetS components and the HR of laryngeal cancer. Of the three MetS components, the combination of elevated FBG, elevated TG, and low HDL was related to the highest risk of laryngeal cancer.
#52 Metabolic Syndrome and Incidence of Laryngeal Cancer: A Nationwide Cohort Study | Scientific Reports
https://www.nature.com/articles/s41598-018-37061-0
Based on previous literatures, Possible mechanism of carcinogenesis of MetS is presumed as belows; (1) insulin resistance and hyperinsulinemia, (2) chronic subclinical inflammation, (3) abnormalities in sex hormones metabolism, (4) damage by endocrine disruptors exposure and air pollution, (5) chronic hyperglycemia, and (6) Disorders of circadian clock. […] Hyperinsulinemia, insulin resistance, and hyperglycemia are increasing proliferation, angiogenesis, damage to the DNA molecule by oxygen active forms due to glucose excess, cellular mobility, and apoptosis. […] It has been suggested that, MetS affects tumor cells cancer and finally increasing the risk of cancer through the change in insulin receptor expression as well as the activation/inactivation of the growth and transcription factors, their receptors. […] Another notable point is the role of insulin growth factor-1 (IGF-1) and insulin receptors which are overstimulated in MetS due to insulin resistance.
#53 Metabolic Syndrome and Incidence of Laryngeal Cancer: A Nationwide Cohort Study | Scientific Reports
https://www.nature.com/articles/s41598-018-37061-0
Based on previous literatures, Possible mechanism of carcinogenesis of MetS is presumed as belows; (1) insulin resistance and hyperinsulinemia, (2) chronic subclinical inflammation, (3) abnormalities in sex hormones metabolism, (4) damage by endocrine disruptors exposure and air pollution, (5) chronic hyperglycemia, and (6) Disorders of circadian clock. […] Hyperinsulinemia, insulin resistance, and hyperglycemia are increasing proliferation, angiogenesis, damage to the DNA molecule by oxygen active forms due to glucose excess, cellular mobility, and apoptosis. […] It has been suggested that, MetS affects tumor cells cancer and finally increasing the risk of cancer through the change in insulin receptor expression as well as the activation/inactivation of the growth and transcription factors, their receptors. […] Another notable point is the role of insulin growth factor-1 (IGF-1) and insulin receptors which are overstimulated in MetS due to insulin resistance.
#54 The Etiology and Pathogenesis of Laryngeal Carcinoma
https://ouci.dntb.gov.ua/en/works/7W0rkkw4/
The Etiology and Pathogenesis of Laryngeal Carcinoma […] Gastroesophageal reflux disease is a risk factor for laryngeal and pharyngeal cancer […] This study provides no evidence in support of the proposed association between gastroesophageal reflux disease and cancers of the larynx or pharynx. […] The data of the current study could not corroborate the hypothesis that gastroesophageal and pharyngolaryngeal refluxes are carcinogenic factors to the laryngopharyngeal mucosa, and more studies are necessary in the future.
#55 Laryngeal cancer: What you should know | MD Anderson Cancer Center
https://www.mdanderson.org/cancerwise/laryngeal-cancer–what-you-should-know.h00-159619434.html
Laryngeal cancer, or larynx cancer, occurs when cancerous cells form in the larynx. […] The biggest risk factor for developing laryngeal cancer is smoking and tobacco use. […] Silent reflux is when stomach acid flows up the esophagus and spills over onto your voice box, explains Diaz. The acid is an irritant that washes away mucus, a protectant. For example, if you smoke, the mucus protects the carcinogens from reaching the mucosa, but if the reflux washes that away, it increases your chance of developing cancer. […] We’re seeing a lot of tumors in the larynx that look like they’re associated with HPV, so it’s important to get vaccinated for HPV if you’re eligible, says Diaz. […] Once the biopsy confirms it’s cancer, we can use a laser to burn off the cancer, says Diaz. This is a very effective option with a high cure rate.
#56 The Etiology and Pathogenesis of Laryngeal Carcinoma
https://ouci.dntb.gov.ua/en/works/7W0rkkw4/
The Etiology and Pathogenesis of Laryngeal Carcinoma […] Gastroesophageal reflux disease is a risk factor for laryngeal and pharyngeal cancer […] This study provides no evidence in support of the proposed association between gastroesophageal reflux disease and cancers of the larynx or pharynx. […] The data of the current study could not corroborate the hypothesis that gastroesophageal and pharyngolaryngeal refluxes are carcinogenic factors to the laryngopharyngeal mucosa, and more studies are necessary in the future.
#57 The etiology and pathogenesis of laryngeal carcinoma – PubMed
https://pubmed.ncbi.nlm.nih.gov/8995133/
Epidemiologic data suggest that the etiology and pathogenesis of laryngeal carcinoma are influenced by environmental and lifestyle-related factors, such as tobacco use, ethanol consumption, and exposure to toxic substances. […] In addition, dietary factors, irradiation, papilloma virus infection, and laryngopharyngeal reflux seem to be significant carcinogenic cofactors. […] This article presents a multi-factorial model of laryngeal mucosal carcinogenesis.
#58 Head and Neck: Laryngeal tumors: an overview
https://atlasgeneticsoncology.org/solid-tumor/5087/head-and-neck-laryngeal-tumors-an-overview
More than 95% of laryngeal tumours are squamous cell carcinomas (SCC). […] The exact cause of laryngeal cancer is still unknown. However, several interrelated co-factors (mainly tobacco smoking and alcohol consumption), are clearly associated with an increased incidence in laryngeal cancer. […] It appears that nicotine is not responsible for cancer itself, but polycyclic aromatic hydrocarbons and nitrosamines are carcinogenic. […] Infections from herpes simplex and HPV, gastroesophageal reflex disease, anatomical malformations, Plummer-Vinson syndrome, steam and heat inhalation, thermal burns and exposure to ionizing radiation, asbestos, nickel, textile fibers and various chemicals, like formaldehyde, vinyl chloride and benzopyrenes, have also been considered as aetiological factors.
#59 Laryngeal Cancer: Diagnosis and Preoperative Work-up | Ento Key
https://entokey.com/laryngeal-cancer-diagnosis-and-preoperative-work-up/
However, these risks decline sharply after smoking cessation although never to the same level as patients who have never smoked. […] While smoking cessation is the single most effective means of preventing laryngeal cancer, it is equally important to encourage patients to quit smoking after the diagnosis of laryngeal cancer has been made. […] Smoking has been identified as an independent risk factor for local recurrence and for recurrence at an earlier time point than those who ceased smoking. […] Additionally, there is a controversial association with chronic gastroesophageal reflux as well as an increased incidence of squamous cell carcinoma in preexisting laryngeal respiratory papillomatosis.
#60 Laryngeal cancer: Symptoms, types, and diagnosis
https://www.medicalnewstoday.com/articles/171568
Laryngeal cancer is a rare cancer in which malignant cells grow in the larynx, or voice box. Smoking tobacco and drinking alcohol are the main risk factors for laryngeal cancer. […] Cancer can develop in any part of the larynx but usually begins in the glottis. Most laryngeal cancers start in the flat, scale-like squamous cells that line the inner walls of the larynx. […] Genetic factors may also play a role in the development of laryngeal cancer. People with Fanconi anemia, which is a condition that causes blood issues from a young age, and dyskeratosis congenita, which is a syndrome that affects the skin, nails, and blood, might be at higher risk of developing many types of head and neck cancer.
#61 Laryngeal Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK526076/
Smoking is the most significant risk factor for laryngeal cancer, accounting for over 70% of all cases. […] Other risk factors for laryngeal cancer include long-term secondhand smoke exposure, male sex, white or black race, genetic and other syndromes, and occupational and environmental exposures. […] The vast majority of laryngeal cancers are squamous cell carcinomas. […] Patterns of spread depend on the location of the primary tumor and the inherent lymphatic supply at that location. Laryngeal cancers are categorized into supraglottic, glottic, and subglottic subsites, with pathophysiology and treatment differing for each subsite. […] Each primary subsite of laryngeal carcinoma carries different implications in symptomatic presentation, patterns of spread, prognosis, and treatment paradigms. […] Early-stage disease is often highly treatable or curable in the supraglottis and glottis, although the prognosis remains poor in the subglottis.
#62 Laryngeal Cancer | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/24035
Smoking is the most significant risk factor for laryngeal cancer, accounting for over 70% of all cases. […] Heavy alcohol consumption is also a risk factor, though its independent effect is unclear due to its frequent combination with tobacco use. […] Other risk factors for laryngeal cancer include long-term secondhand smoke exposure, male sex, white or black race, genetic and other syndromes, and occupational and environmental exposures. […] The vast majority of laryngeal cancers are squamous cell carcinomas. […] Patterns of spread depend on the location of the primary tumor and the inherent lymphatic supply at that location. […] Laryngeal cancers are categorized into supraglottic, glottic, and subglottic subsites, with pathophysiology and treatment differing for each subsite. […] Early lymphatic involvement is a hallmark of supraglottic cancers, with 55% of patients showing clinical evidence of nodal metastasis at presentation.
#63 Laryngeal Cancer – StatPearls – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK526076/
Smoking is the most significant risk factor for laryngeal cancer, accounting for over 70% of all cases. […] Other risk factors for laryngeal cancer include long-term secondhand smoke exposure, male sex, white or black race, genetic and other syndromes, and occupational and environmental exposures. […] The vast majority of laryngeal cancers are squamous cell carcinomas. […] Patterns of spread depend on the location of the primary tumor and the inherent lymphatic supply at that location. Laryngeal cancers are categorized into supraglottic, glottic, and subglottic subsites, with pathophysiology and treatment differing for each subsite. […] Each primary subsite of laryngeal carcinoma carries different implications in symptomatic presentation, patterns of spread, prognosis, and treatment paradigms. […] Early-stage disease is often highly treatable or curable in the supraglottis and glottis, although the prognosis remains poor in the subglottis.
#64 Squamous cell carcinoma of the larynx | Radiology Reference Article | Radiopaedia.org
https://radiopaedia.org/articles/squamous-cell-carcinoma-of-the-larynx?lang=us
Squamous cell carcinoma (SCC) accounts for 98% of laryngeal tumors. […] SCC arises from the epiglottis, aryepiglottic fold, false vocal fold, as well as the deep pre-epiglottic and paraglottic space. It metastasizes early to cervical lymph nodes. […] SCC arises from the true vocal fold. It manifests early due to hoarseness of voice and rarely metastasizes due to the poor lymphatic drainage of the glottis. […] SCC arises from anywhere below the true vocal fold to the inferior edge of the cricoid cartilage. It produces minimal symptoms, which is responsible for its late diagnosis, which coupled with early lymph node metastasis, means a poor prognosis.
#65 Laryngeal Cancer | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/24035
Smoking is the most significant risk factor for laryngeal cancer, accounting for over 70% of all cases. […] Heavy alcohol consumption is also a risk factor, though its independent effect is unclear due to its frequent combination with tobacco use. […] Other risk factors for laryngeal cancer include long-term secondhand smoke exposure, male sex, white or black race, genetic and other syndromes, and occupational and environmental exposures. […] The vast majority of laryngeal cancers are squamous cell carcinomas. […] Patterns of spread depend on the location of the primary tumor and the inherent lymphatic supply at that location. […] Laryngeal cancers are categorized into supraglottic, glottic, and subglottic subsites, with pathophysiology and treatment differing for each subsite. […] Early lymphatic involvement is a hallmark of supraglottic cancers, with 55% of patients showing clinical evidence of nodal metastasis at presentation.
#66 Laryngeal Cancer: Diagnosis and Preoperative Work-up | Ento Key
https://entokey.com/laryngeal-cancer-diagnosis-and-preoperative-work-up/
Laryngeal carcinoma is the eleventh-most common form of cancer among men worldwide and is the second-most common malignancy of the head and neck. […] Effective treatment and understanding of laryngeal cancer requires fundamental knowledge of the complex anatomy of this region. […] These divisions have clinical relevance in that they help predict the clinical behavior and pattern of spread of the tumor. […] The supraglottis develops from the midline buccopharyngeal anlage from branchial arches 4 and 6 with rich bilateral lymphatics. Clinically, this translates to a significant incidence of unilateral or bilateral cervical metastasis 25% to 75% for all T-stages. […] In contrast to the supraglottic structures, the glottis forms from the midline fusion of lateral structures derived from the tracheobronchial anlage from arches 4, 5, and 6 and has a relative dearth of lymphatics. Consequently, this embryologic boundary limits submucosal spread to adjacent sites within the larynx for early stage cancers, and the paucity of lymphatic in the glottis contains lymphatic spread to the neck allowing glottic cancers to remain localized to the larynx for longer periods of time.
#67 Malignant Tumors of the Larynx: Practice Essentials, History Of The Procedure, Problem
https://emedicine.medscape.com/article/848592-overview
Malignant tumors of the larynx may affect laryngeal physiology depending on tumor location and size. Supraglottic tumors may not alter laryngeal function until they reach a relatively large size, at which time airway obstruction may be the first symptom. Conversely, glottic tumors alter voice quality early in their development and are thus often discovered at an early stage. […] Development and progression of malignant tumors of the larynx occurs at the molecular and histologic level. The molecular steps involved in tumorigenesis have not been fully elucidated and likely vary from patient to patient. Histologic progression occurs from normal laryngeal mucosa to dysplastic mucosa to carcinoma in situ to invasive carcinoma. This progression is a multistep process of accumulated genetic events that lead to the development of larynx tumors.
#68 Squamous cell carcinoma of the larynx | Radiology Reference Article | Radiopaedia.org
https://radiopaedia.org/articles/squamous-cell-carcinoma-of-the-larynx?lang=us
Squamous cell carcinoma (SCC) accounts for 98% of laryngeal tumors. […] SCC arises from the epiglottis, aryepiglottic fold, false vocal fold, as well as the deep pre-epiglottic and paraglottic space. It metastasizes early to cervical lymph nodes. […] SCC arises from the true vocal fold. It manifests early due to hoarseness of voice and rarely metastasizes due to the poor lymphatic drainage of the glottis. […] SCC arises from anywhere below the true vocal fold to the inferior edge of the cricoid cartilage. It produces minimal symptoms, which is responsible for its late diagnosis, which coupled with early lymph node metastasis, means a poor prognosis.
#69 Malignant Tumors of the Larynx: Practice Essentials, History Of The Procedure, Problem
https://emedicine.medscape.com/article/848592-overview
Malignant tumors of the larynx may affect laryngeal physiology depending on tumor location and size. Supraglottic tumors may not alter laryngeal function until they reach a relatively large size, at which time airway obstruction may be the first symptom. Conversely, glottic tumors alter voice quality early in their development and are thus often discovered at an early stage. […] Development and progression of malignant tumors of the larynx occurs at the molecular and histologic level. The molecular steps involved in tumorigenesis have not been fully elucidated and likely vary from patient to patient. Histologic progression occurs from normal laryngeal mucosa to dysplastic mucosa to carcinoma in situ to invasive carcinoma. This progression is a multistep process of accumulated genetic events that lead to the development of larynx tumors.
#70 Laryngeal Cancer: Diagnosis and Preoperative Work-up | Ento Key
https://entokey.com/laryngeal-cancer-diagnosis-and-preoperative-work-up/
Laryngeal carcinoma is the eleventh-most common form of cancer among men worldwide and is the second-most common malignancy of the head and neck. […] Effective treatment and understanding of laryngeal cancer requires fundamental knowledge of the complex anatomy of this region. […] These divisions have clinical relevance in that they help predict the clinical behavior and pattern of spread of the tumor. […] The supraglottis develops from the midline buccopharyngeal anlage from branchial arches 4 and 6 with rich bilateral lymphatics. Clinically, this translates to a significant incidence of unilateral or bilateral cervical metastasis 25% to 75% for all T-stages. […] In contrast to the supraglottic structures, the glottis forms from the midline fusion of lateral structures derived from the tracheobronchial anlage from arches 4, 5, and 6 and has a relative dearth of lymphatics. Consequently, this embryologic boundary limits submucosal spread to adjacent sites within the larynx for early stage cancers, and the paucity of lymphatic in the glottis contains lymphatic spread to the neck allowing glottic cancers to remain localized to the larynx for longer periods of time.
#71 Laryngeal Cancer: Diagnosis and Preoperative Work-up | Ento Key
https://entokey.com/laryngeal-cancer-diagnosis-and-preoperative-work-up/
Laryngeal carcinoma is the eleventh-most common form of cancer among men worldwide and is the second-most common malignancy of the head and neck. […] Effective treatment and understanding of laryngeal cancer requires fundamental knowledge of the complex anatomy of this region. […] These divisions have clinical relevance in that they help predict the clinical behavior and pattern of spread of the tumor. […] The supraglottis develops from the midline buccopharyngeal anlage from branchial arches 4 and 6 with rich bilateral lymphatics. Clinically, this translates to a significant incidence of unilateral or bilateral cervical metastasis 25% to 75% for all T-stages. […] In contrast to the supraglottic structures, the glottis forms from the midline fusion of lateral structures derived from the tracheobronchial anlage from arches 4, 5, and 6 and has a relative dearth of lymphatics. Consequently, this embryologic boundary limits submucosal spread to adjacent sites within the larynx for early stage cancers, and the paucity of lymphatic in the glottis contains lymphatic spread to the neck allowing glottic cancers to remain localized to the larynx for longer periods of time.
#72 Laryngeal Cancer | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/24035
Glottic tumors do not pose a risk of lymphatic involvement unless there is a supraglottic or glottic extension. […] The subglottis extends from 5 mm below the free margin of the vocal cord superiorly to the inferior border of the cricoid cartilage. […] The overall prognosis for laryngeal cancer is intimately linked to the stage of disease at the time of treatment. […] The overall 5-year survival rate for laryngeal cancer in the United States is 61%. […] If the cancer is confined to the larynx, the overall 5-year survival is 78%. […] The overall prognosis being the best for glottic cancer, followed by supraglottic and then subglottic tumors.
#73 Laryngeal Cancer | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/24035
Glottic tumors do not pose a risk of lymphatic involvement unless there is a supraglottic or glottic extension. […] The subglottis extends from 5 mm below the free margin of the vocal cord superiorly to the inferior border of the cricoid cartilage. […] The overall prognosis for laryngeal cancer is intimately linked to the stage of disease at the time of treatment. […] The overall 5-year survival rate for laryngeal cancer in the United States is 61%. […] If the cancer is confined to the larynx, the overall 5-year survival is 78%. […] The overall prognosis being the best for glottic cancer, followed by supraglottic and then subglottic tumors.
#74 Laryngeal Cancer | Treatment & Management | Point of Care
https://www.statpearls.com/point-of-care/24035
Glottic tumors do not pose a risk of lymphatic involvement unless there is a supraglottic or glottic extension. […] The subglottis extends from 5 mm below the free margin of the vocal cord superiorly to the inferior border of the cricoid cartilage. […] The overall prognosis for laryngeal cancer is intimately linked to the stage of disease at the time of treatment. […] The overall 5-year survival rate for laryngeal cancer in the United States is 61%. […] If the cancer is confined to the larynx, the overall 5-year survival is 78%. […] The overall prognosis being the best for glottic cancer, followed by supraglottic and then subglottic tumors.
#75
http://www.bccancer.bc.ca/health-info/types-of-cancer/head-neck/larynx
Laryngeal cancer starts in the larynx. The larynx is located just above your trachea (windpipe). It is also called the voice box. […] If laryngeal cancer is found and treated early, it is very curable. This type of cancer grows slowly. […] Most laryngeal cancers are carcinomas. These are cancers that start in the cells that line the larynx (squamous cells). How the cancer grows depends on where it starts. […] The most common type of laryngeal cancer is cancer of the vocal cords (glottis). These usually grow slowly. In the early stage, they do not usually spread to other parts of the body. […] Cancers of the subglottis are rare. Only 1-8% (1-8 in 100) of all laryngeal cancers are this type. This type of cancer is most likely to spread to other parts of the body in the early stages. […] Cancers of the supraglottis are also rare. They are likely to spread, usually to the lymph nodes in the neck.
#76 Squamous cell carcinoma of the larynx | Radiology Reference Article | Radiopaedia.org
https://radiopaedia.org/articles/squamous-cell-carcinoma-of-the-larynx?lang=us
Squamous cell carcinoma (SCC) accounts for 98% of laryngeal tumors. […] SCC arises from the epiglottis, aryepiglottic fold, false vocal fold, as well as the deep pre-epiglottic and paraglottic space. It metastasizes early to cervical lymph nodes. […] SCC arises from the true vocal fold. It manifests early due to hoarseness of voice and rarely metastasizes due to the poor lymphatic drainage of the glottis. […] SCC arises from anywhere below the true vocal fold to the inferior edge of the cricoid cartilage. It produces minimal symptoms, which is responsible for its late diagnosis, which coupled with early lymph node metastasis, means a poor prognosis.
#77
http://www.bccancer.bc.ca/health-info/types-of-cancer/head-neck/larynx
Laryngeal cancer starts in the larynx. The larynx is located just above your trachea (windpipe). It is also called the voice box. […] If laryngeal cancer is found and treated early, it is very curable. This type of cancer grows slowly. […] Most laryngeal cancers are carcinomas. These are cancers that start in the cells that line the larynx (squamous cells). How the cancer grows depends on where it starts. […] The most common type of laryngeal cancer is cancer of the vocal cords (glottis). These usually grow slowly. In the early stage, they do not usually spread to other parts of the body. […] Cancers of the subglottis are rare. Only 1-8% (1-8 in 100) of all laryngeal cancers are this type. This type of cancer is most likely to spread to other parts of the body in the early stages. […] Cancers of the supraglottis are also rare. They are likely to spread, usually to the lymph nodes in the neck.
#78 Laryngeal Cancer: Diagnosis and Preoperative Work-up | Ento Key
https://entokey.com/laryngeal-cancer-diagnosis-and-preoperative-work-up/
Except for advance stage tumors, most laryngeal cancers tend to remain confined to one anatomic site because of the pushing mechanism of tumor growth. […] Additionally, cartilaginous and fascial anatomic structures, such as the thyroid and cricoid cartilages with their overlying perichondrium, the ventricle, the conus elasticus, the quadrangular and thyrohyoid membranes, and the hyoepiglottic ligament, act as barriers to spread. […] The anterior commisure and thyrohyoid membrane, in contradistinction to the above structures, offers little resistance to tumor spread. […] Eighty-five percent of laryngeal cancers can be attributed to tobacco and alcohol use. Smoking is the predominant risk factor for laryngeal carcinoma with alcohol use being an independent and synergistic risk factor. […] Current smokers have a 10- to 20-fold increased risk of laryngeal cancer compared with nonsmokers.
#79 Laryngeal Cancer: Diagnosis and Preoperative Work-up | Ento Key
https://entokey.com/laryngeal-cancer-diagnosis-and-preoperative-work-up/
Except for advance stage tumors, most laryngeal cancers tend to remain confined to one anatomic site because of the pushing mechanism of tumor growth. […] Additionally, cartilaginous and fascial anatomic structures, such as the thyroid and cricoid cartilages with their overlying perichondrium, the ventricle, the conus elasticus, the quadrangular and thyrohyoid membranes, and the hyoepiglottic ligament, act as barriers to spread. […] The anterior commisure and thyrohyoid membrane, in contradistinction to the above structures, offers little resistance to tumor spread. […] Eighty-five percent of laryngeal cancers can be attributed to tobacco and alcohol use. Smoking is the predominant risk factor for laryngeal carcinoma with alcohol use being an independent and synergistic risk factor. […] Current smokers have a 10- to 20-fold increased risk of laryngeal cancer compared with nonsmokers.
#80 Laryngeal Cancer: Diagnosis and Preoperative Work-up | Ento Key
https://entokey.com/laryngeal-cancer-diagnosis-and-preoperative-work-up/
Except for advance stage tumors, most laryngeal cancers tend to remain confined to one anatomic site because of the pushing mechanism of tumor growth. […] Additionally, cartilaginous and fascial anatomic structures, such as the thyroid and cricoid cartilages with their overlying perichondrium, the ventricle, the conus elasticus, the quadrangular and thyrohyoid membranes, and the hyoepiglottic ligament, act as barriers to spread. […] The anterior commisure and thyrohyoid membrane, in contradistinction to the above structures, offers little resistance to tumor spread. […] Eighty-five percent of laryngeal cancers can be attributed to tobacco and alcohol use. Smoking is the predominant risk factor for laryngeal carcinoma with alcohol use being an independent and synergistic risk factor. […] Current smokers have a 10- to 20-fold increased risk of laryngeal cancer compared with nonsmokers.
#81 Cancer of the Larynx | CancerIndex
http://www.cancerindex.org/clinks2y.htm
The enforced expression of RUNX3 inhibited LSCC cell migration, invasion, and proliferation, whereas the inhibition of RUNX3 did the opposite. […] We revealed a previously unknown function of TRPP2 in cancer development and a TRPP2-dependent mechanism underlying laryngocarcinoma cell invasion and metastasis. […] Our results suggest that TRPP2 may be used as a biomarker for evaluating patient prognosis and as a novel therapeutic target in HLSCC. […] The presence of pharyngeal invasion, pathologically confirmed node-positive stage 2-3 disease, close or microscopic positive margins, and lymphovascular and perineural invasion have a negative impact on prognosis. […] Together, our data indicated that fisetin had a potential role in controlling human laryngeal cancer through inhibiting tumor cell proliferation, inducing apoptosis and autophagy regulated by ERK1/2 and AKT/NF-B/mTOR signaling pathways, which might provide a therapeutic strategy for laryngeal cancer inhibition in future.
#82 Laryngeal Cancer: Symptoms, Causes & Treatment
https://my.clevelandclinic.org/health/diseases/16611-laryngeal-cancer
Cancer affecting your larynx or vocal cords happens when cells grow uncontrollably in your larynx. As these cancerous (malignant) cells multiply, they invade tissues and damage your body. […] Some forms of HPV (human papillomavirus), a sexually transmitted infection (STI), can cause laryngeal cancer. […] You also have a much higher chance of developing it if you use tobacco or drink alcohol frequently. […] Smoking or using other tobacco products greatly increases your risk of developing laryngeal cancer. Drinking alcohol, especially a lot of it (more than one drink daily) also raises your risk. And using alcohol and tobacco together increases your risk even more. […] Laryngeal cancer that spreads beyond your larynx may invade your thyroid, windpipe (trachea), esophagus, tongue, lungs, liver and bones.
#83 Laryngeal Cancer – Ear, Nose, and Throat Disorders – Merck Manual Professional Edition
https://www.merckmanuals.com/professional/ear-nose-and-throat-disorders/tumors-of-the-head-and-neck/laryngeal-cancer
Ninety percent of laryngeal cancer is squamous cell carcinoma. Smoking, excessive alcohol use, lower socioeconomic status, and being male and 60 years increase risk. Squamous cell carcinoma is the most common cancer of the larynx. Over 95% of patients smoke; 15 pack-years of smoking increase the risk 30-fold. Lymph node metastasis are more common in supraglottic and subglottic tumors than with glottic cancers due to the minimal lymphatic drainage of the glottis and because glottic tumors cause symptoms earlier. Distant metastases occur most frequently in the lungs and liver. Common sites of origin are the true vocal cords (glottis) and the supraglottic larynx. The least common site is the subglottic larynx, where only 1% of primary laryngeal cancers originate. The approach to treatment varies by anatomic location (ie, supraglottis, glottis, subglottis) and stage. Early supraglottic carcinoma can be effectively treated with radiation therapy or partial laryngectomy. Most advanced-stage supraglottic cancers initially are treated with chemotherapy and radiation therapy. Early-stage glottic carcinoma is treated with laser excision, radiation therapy, or occasionally open laryngeal surgery. For moderately advanced glottic carcinoma, defined by a lack of vocal cord mobility or extension into the tongue, most patients are treated with both chemotherapy and radiation therapy. Early subglottic carcinoma is rarely treatable with endoscopic resection so radiation is the mainstay of treatment. For more advanced subglottic lesions or lesions with metastasis, chemoradiation is the standard of care unless there is extension outside of the larynx or extensive cartilage invasion in which case total laryngectomy provides the best outcome. The overall relative 5-year survival rate for patients with laryngeal cancer is 61%. Early-stage glottic carcinoma has an 85 to 95% 5-year survival rate. Patients who present with regional nodal disease have a 48% relative 5-year survival rate, and those who present with distant metastases have a 34% relative 5-year survival rate.
#84 Releasing the brakes: the role of immune checkpoint inhibitors in laryngeal cancer
https://www.explorationpub.com/Journals/etat/Article/1002292
Laryngeal cancer, a subtype of head and neck cancer, poses significant challenges due to its profound impact on essential functions such as speech and swallowing and poor survival rates in advanced stages. […] Immune checkpoint inhibitors (ICIs) have revolutionized oncology by countering tumor-induced immune evasion, restoring immune surveillance, and activating T-cell responses against cancer. […] Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape for cancer, offering new hope for improved survival. ICIs function by blocking checkpoint molecules, such as PD-1 (programmed cell death-1), PD-L1 (programmed death-ligand 1), and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), which tumors exploit to evade immune detection. […] By targeting these pathways, ICIs help reactivate the immune system, enabling it to recognize and attack cancer cells.
#85 Releasing the brakes: the role of immune checkpoint inhibitors in laryngeal cancer
https://www.explorationpub.com/Journals/etat/Article/1002292
Laryngeal cancer, a subtype of head and neck cancer, poses significant challenges due to its profound impact on essential functions such as speech and swallowing and poor survival rates in advanced stages. […] Immune checkpoint inhibitors (ICIs) have revolutionized oncology by countering tumor-induced immune evasion, restoring immune surveillance, and activating T-cell responses against cancer. […] Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape for cancer, offering new hope for improved survival. ICIs function by blocking checkpoint molecules, such as PD-1 (programmed cell death-1), PD-L1 (programmed death-ligand 1), and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), which tumors exploit to evade immune detection. […] By targeting these pathways, ICIs help reactivate the immune system, enabling it to recognize and attack cancer cells.
#86 Releasing the brakes: the role of immune checkpoint inhibitors in laryngeal cancer
https://www.explorationpub.com/Journals/etat/Article/1002292
The approval of ICIs, namely nivolumab and pembrolizumab, for the treatment of laryngeal cancer has been supported by the following clinical trials demonstrating their efficacy in advanced HNSCC. […] The integration of ICIs with established treatment modalities is set to revolutionize the management of laryngeal cancer, moving toward a patient-centered future in laryngeal cancer therapy.
#87 Releasing the brakes: the role of immune checkpoint inhibitors in laryngeal cancer
https://www.explorationpub.com/Journals/etat/Article/1002292
The approval of ICIs, namely nivolumab and pembrolizumab, for the treatment of laryngeal cancer has been supported by the following clinical trials demonstrating their efficacy in advanced HNSCC. […] The integration of ICIs with established treatment modalities is set to revolutionize the management of laryngeal cancer, moving toward a patient-centered future in laryngeal cancer therapy.
#88 Head and Neck: Laryngeal tumors: an overview
https://atlasgeneticsoncology.org/solid-tumor/5087/head-and-neck-laryngeal-tumors-an-overview
Alterations of p53 protein expression and mutations of the p53 gene have been proposed as independent predictors of recurrence in LSCC, however with controversial prognostic value. […] In LSCC, degradation mediated by other cellular proteins, such as MDM2 or by human papillomavirus (HPV) E6 oncoprotein may represent alternative pathways leading to loss of p53 function. […] A p53 gene therapy approach has already been shown to induce apoptosis, radio- and chemosensitisation in cell lines and this, in combination with radiotherapy or chemotherapy, is a rational possibility.
#89 Effect of HPV Infection on the Occurrence and Development of Laryngeal Cancer: A Review
https://www.jcancer.org/v10p4455.htm
The mRNA expression of HR-HPV plays an important role in the development and progression of laryngeal cancer. […] HPV infection induces laryngeal cancer mainly because of excessive expression of HR-HPV E6 and E7 proteins. […] The occurrence and development of laryngeal cancer is closely related to the overexpression of HPV16 E7 protein and cyclin D1. […] Studies have shown that after HR-HPV16 and 18 infect the larynx, the early gene product E6 protein can bind with p53 protein and form a complex resulting in p53 inactivation and thus hindering the role of p53 protein in tumor inhibition in cells. […] The functional classification of p53 mutants based on EAp53 can predict the disease-specific survival rate with advanced laryngeal cancer and p53 mutation. […] The expression of p16 protein is slightly lower in laryngeal carcinoma than benign laryngeal lesions and significantly lower than in vocal polyps. […] Therefore, we must deeply study the molecular mechanism of laryngeal cancer caused by HPV infection.
#90 Role and mechanism of miR-548-3p/ DAG1 in the occurrence and malignant transformation of laryngeal carcinoma.
http://ve.scielo.org/scielo.php?script=sci_arttext&pid=S0535-51332022000300206
Role and mechanism of miR-548-3p/ DAG1 in the occurrence and malignant transformation of laryngeal carcinoma. […] The AMC-HN-8 cell line and the primary human laryngeal epithelial cell lines were utilized in this work to explore the molecular mechanism of miR-548-3p regulating the gene DAG1 to induce the occurrence and malignant transformation of laryngeal carcinoma. […] Through carrying out research on the cellular levels, our work has demonstrated that miR-548-3p regulated the content of protein DAG1, and then further induced malignant transformation of laryngeal carcinoma. […] To explore the role and mechanism of miR-548-3p/DAG1 in the occurrence and malignant transformation of laryngeal carcinoma, the human laryngeal carcinoma cell line AMC-HN-8 and the primary human laryngeal epithelial cell line were utilized here. We found that the non-coding RNA miR-548-3p can target and regulate the gene DAG1, and then further induce malignant transformation of laryngeal carcinoma.
#91 Role and mechanism of miR-548-3p/ DAG1 in the occurrence and malignant transformation of laryngeal carcinoma.
http://ve.scielo.org/scielo.php?script=sci_arttext&pid=S0535-51332022000300206
The essence of malignant tumors is abnormal cell proliferation, which locally invades surrounding normal tissues, and even metastasizes to other parts of the body through the circulatory system. […] This project aims to promote the development of diagnosis and treatment of laryngeal cancer by identifying the underlying molecular mechanism of laryngeal cancer exacerbation. […] This work has indicated that miR-548-3p indirectly participates in the various processes of malignant transformation of laryngeal cancer by regulating the expression of DAG1. […] The direct action of DAG1 with the proteins LAMA2 and UTRN enhances the proliferation, migration and invasion ability of laryngeal cancer cells, thereby increasing the malignant degree of laryngeal cancer in all directions. […] In summary, this experiment controlled the expression of miR-548-3p by adding different plasmids, and then controlled the expression of protein DAG1, and finally achieved the effect of controlling the malignant degree of laryngeal cancer.
#92 Downregulation of circ-RANBP9 in laryngeal cancer and its clinical significance
https://atm.amegroups.org/article/view/65817/html
Laryngeal cancer (LC) is a common malignant tumor of the head and neck. The initiation and progression of LC is a complicated process driven by various pathogenetic factors and dysregulation of multiple genes. […] Currently, surgery and radiotherapy are the main treatment methods for LC, but the results of these treatments are frequently unsatisfactory. […] The majority of previous studies have shown that circRNAs act as microRNA sponges, which regulate tumorigenesis though ceRNA network. […] Our study showed that circ-RANBP9 inhibited the proliferation, invasion, and migration of LC cells. […] The results indicated that circ-RANBP9 inhibited the metastasis of laryngeal cancer. […] The pathways mentioned above have been shown to be dysregulated in multiple malignant tumors. […] Our results showed that circ-RANBP9 expression was lower in LC and that it exerted anticancer activity. […] These results suggest that circ-RANBP9 may participate in the signaling pathways mentioned above. […] Our findings may therefore improve the early diagnosis, early treatment, and overall prognosis for LC.
#93 Downregulation of circ-RANBP9 in laryngeal cancer and its clinical significance
https://atm.amegroups.org/article/view/65817/html
Laryngeal cancer (LC) is a common malignant tumor of the head and neck. The initiation and progression of LC is a complicated process driven by various pathogenetic factors and dysregulation of multiple genes. […] Currently, surgery and radiotherapy are the main treatment methods for LC, but the results of these treatments are frequently unsatisfactory. […] The majority of previous studies have shown that circRNAs act as microRNA sponges, which regulate tumorigenesis though ceRNA network. […] Our study showed that circ-RANBP9 inhibited the proliferation, invasion, and migration of LC cells. […] The results indicated that circ-RANBP9 inhibited the metastasis of laryngeal cancer. […] The pathways mentioned above have been shown to be dysregulated in multiple malignant tumors. […] Our results showed that circ-RANBP9 expression was lower in LC and that it exerted anticancer activity. […] These results suggest that circ-RANBP9 may participate in the signaling pathways mentioned above. […] Our findings may therefore improve the early diagnosis, early treatment, and overall prognosis for LC.
#94 Laryngeal Cancer Treatment – NCI
https://www.cancer.gov/types/head-and-neck/patient/adult/laryngeal-treatment-pdq
When cancer spreads to another part of the body, it is called metastasis. […] The metastatic tumor is the same type of cancer as the primary tumor. For example, if laryngeal cancer spreads to the lung, the cancer cells in the lung are actually laryngeal cancer cells. […] Many cancer deaths are caused when cancer moves from the original tumor and spreads to other tissues and organs. This is called metastatic cancer. […] Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. […] Radiosensitizers are drugs that make tumor cells more sensitive to radiation therapy. Combining radiation therapy with radiosensitizers may kill more tumor cells.
#95 Laryngeal Cancer: Symptoms, Causes & Treatment
https://my.clevelandclinic.org/health/diseases/16611-laryngeal-cancer
Treatment for laryngeal cancer includes: Radiation therapy: Radiation oncologists deliver high-energy radiation beams to kill cancer cells. The radiation targets only the tumor to minimize damage to surrounding healthy tissue. […] Chemotherapy: Medical oncologists use medications to kill or slow the growth of cancer cells. […] Immunotherapy: This treatment uses your immune system, your body’s natural defenses, to help fight cancer. […] Targeted therapy: This treatment targets cancer cells with specific types of proteins, preventing the cells from multiplying. […] For early laryngeal cancer, your care team will likely recommend surgery or radiation therapy. Research has shown that both are effective. […] If you smoke, it’s important to quit. Don’t smoke before or during treatment, and stay tobacco-free even after you finish treatment. People who smoke after treatment have a higher chance of developing another type of cancer. […] But even advanced laryngeal cancer can be cured. If it comes back, it usually happens within the first two or three years after treatment.
#96 Laryngeal Cancer Treatment – NCI
https://www.cancer.gov/types/head-and-neck/patient/adult/laryngeal-treatment-pdq
When cancer spreads to another part of the body, it is called metastasis. […] The metastatic tumor is the same type of cancer as the primary tumor. For example, if laryngeal cancer spreads to the lung, the cancer cells in the lung are actually laryngeal cancer cells. […] Many cancer deaths are caused when cancer moves from the original tumor and spreads to other tissues and organs. This is called metastatic cancer. […] Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. […] Radiosensitizers are drugs that make tumor cells more sensitive to radiation therapy. Combining radiation therapy with radiosensitizers may kill more tumor cells.
#97 Cancer of larynx and laryngeal cancer ppt | PPT
https://www.slideshare.net/slideshow/cancer-of-larynx-and-laryngeal-cancer-ppt/237737121
New types of treatment are being tested in clinical trials, including chemoprevention, which is the use of drugs, vitamins, or other substances to reduce the risk of developing cancer or reduce the risk of cancer recurrence. […] In India, laryngeal cancer contributes to approximately 3-6% of all cancers in men. The age-adjusted incidence rate of cancer larynx in males varies widely among registries. Indian studies show tobacco, alcohol, long-term exposure to indoor air pollution, spicy food, and nonvegetarian diet as risk factors for laryngeal cancer. […] There is wide regional variation in the incidence of laryngeal cancer in India. Survival rates of laryngeal carcinoma are much lower as compared to other Asian countries. Studies conducted in India to identify important risk factors of laryngeal cancer are very limited, especially on diet and indoor air pollution. Hence, more research is required for identifying the etiological factors and development of scientifically sound laryngeal cancer prevention programs.