Rak prącia – Epidemiologia

Rak prącia
Epidemiologia

Rak prącia jest rzadkim nowotworem złośliwym, stanowiącym około 0,8 przypadków na 100 000 mężczyzn rocznie globalnie, z dominującą postacią raka płaskonabłonkowego (>95%). Występowanie wykazuje znaczne zróżnicowanie geograficzne, z wyższą zachorowalnością w krajach rozwijających się (np. Brazylia 2,8-6,8/100 000, Indie 0,7-3,0/100 000) w porównaniu do krajów uprzemysłowionych (Europa 0,94/100 000, USA 0,5/100 000). Szczyt zachorowań przypada na 6. i 7. dekadę życia, choć 22% pacjentów to osoby poniżej 40 lat. Kluczowymi czynnikami ryzyka są zakażenie HPV (obecne w 40-50% przypadków, głównie HPV-16), stulejka (OR 4,9-7,2), palenie tytoniu (2,4-krotnie zwiększone ryzyko), przewlekłe stany zapalne (np. liszaj twardzinowy) oraz niski status społeczno-ekonomiczny. Obrzezanie noworodkowe wykazuje silny efekt ochronny (OR 0,33). Wzrost zachorowalności obserwuje się w niektórych krajach europejskich i USA, a prognozy GLOBOCAN przewidują wzrost o ponad 56% do 2040 roku.

Epidemiologia raka prącia

Rak prącia jest stosunkowo rzadkim nowotworem złośliwym narządów moczowo-płciowych mężczyzn. Według danych Międzynarodowej Agencji Badań nad Rakiem (IARC) w 2020 roku na całym świecie zdiagnozowano 36 068 nowych przypadków raka prącia, co stanowi około 0,8 przypadku na 100 000 mężczyzn rocznie (standaryzowany według wieku współczynnik zachorowalności). Tym samym rak prącia zajmuje 30. miejsce na liście najczęstszych nowotworów na świecie.¹²³⁴ Zdecydowana większość (ponad 95%) przypadków raka prącia to rak płaskonabłonkowy (squamous cell carcinoma – SCC).¹⁵

Różnice geograficzne w zachorowalności

Występowanie raka prącia charakteryzuje się znaczącym zróżnicowaniem geograficznym. W krajach uprzemysłowionych, takich jak Stany Zjednoczone i Europa, choroba ta występuje stosunkowo rzadko, z ogólnym współczynnikiem zachorowalności wynoszącym około 0,94/100 000 mężczyzn w Europie i 0,5 w USA.⁵ W Stanach Zjednoczonych rak prącia stanowi mniej niż 1% wszystkich nowotworów u mężczyzn, z roczną liczbą przypadków szacowaną na około 2 190 nowych zachorowań i 510 zgonów w 2025 roku.⁶⁷

W przeciwieństwie do krajów rozwiniętych, w krajach rozwijających się, takich jak Ameryka Południowa, Afryka i Indie, częstość występowania jest znacznie wyższa i może stanowić nawet do 12% nowotworów złośliwych u mężczyzn.⁵ Najwyższe wskaźniki zachorowalności odnotowuje się w:

Brazylii (od 2,8 do 6,8 na 100 000 mężczyzn)⁸⁹
Indiach (0,7-3,0 na 100 000)⁵
Niektórych częściach Afryki, np. Ugandzie (2,8 na 100 000)¹⁰

Stan Maranhão w północno-wschodniej Brazylii ma najwyższy na świecie wskaźnik zachorowalności na raka prącia, wynoszący 6,1 przypadków na 100 000 mieszkańców.⁹¹¹ W Hiszpanii odnotowano wyższy niż średni europejski wskaźnik zachorowalności wynoszący 2,55/100 000 mężczyzn rocznie (dane z 2015 r.).¹²

Interesujące różnice obserwuje się również w Indonezji, gdzie wyspa Bali ma wyjątkowo wysoką koncentrację przypadków raka prącia (45% wszystkich przypadków w kraju), ze średnim standaryzowanym według wieku współczynnikiem zachorowalności (ASR) wynoszącym 2,1 na 100 000 mężczyzn, podczas gdy w innych prowincjach wskaźnik ten wynosi poniżej 1 na 100 000.¹³

Trendy czasowe w zachorowalności

Obserwuje się zróżnicowane trendy w zakresie zachorowalności na raka prącia w różnych regionach świata. W Wielkiej Brytanii odnotowano wzrost zachorowalności o 28% między 1993 a 2018 rokiem, a standaryzowane według wieku wskaźniki zachorowalności (European age-standardised rates) zwiększyły się o 37% między okresami 1993-1995 a 2017-2019.⁵¹⁴ Prognozy sugerują, że do 2038-2040 roku może być około 1 100 nowych przypadków raka prącia rocznie w Wielkiej Brytanii, co oznacza wzrost o 9% w porównaniu z okresem 2023-2025.¹⁵

W Norwegii zaobserwowano wzrost standaryzowanych według wieku wskaźników zachorowalności w okresach 5-letnich od 2001-2015 w porównaniu z poprzednimi okresami (0,65/100 000 w latach 1956-60 w porównaniu do 0,91/100 000 w latach 2011-2015), ze Szacowaną Roczną Zmianą Procentową (Estimated Annual Percent Change) wynoszącą +0,80%.⁵

W USA trend był początkowo malejący – ogólny standaryzowany według wieku wskaźnik zachorowalności zmniejszył się między 1973 a 2002 rokiem: z 0,84 (1973-1982), do 0,69 (1983-1992) i 0,58 (1993-2002) na 100 000 mężczyzn. Jednak nowsze dane z lat 2004-2016 pokazują odwrócenie trendu z szacowaną roczną zmianą procentową wynoszącą +3,5%.⁵

Według narzędzia prognostycznego GLOBOCAN Cancer Tomorrow, zachorowalność na raka prącia na świecie jest przewidywana do wzrostu o ponad 56% do 2040 roku.³

Różnice demograficzne w zachorowalności

Rak prącia dotyka głównie mężczyzn w starszym wieku, przy czym szczyt zachorowalności przypada na szóstą i siódmą dekadę życia (60-70 lat).¹⁴ W Wielkiej Brytanii około jednej trzeciej nowych przypadków (32%) diagnozuje się u mężczyzn w wieku 75 lat i starszych. Wskaźniki zachorowalności specyficzne dla wieku rosną stopniowo od około 25-29 lat, bardziej gwałtownie od 40-44 lat i nadal wzrastają wraz z wiekiem, osiągając najwyższe wartości w grupie wiekowej 90+.¹⁴ Niemniej jednak, nowotwór może wystąpić również u młodszych mężczyzn – w niektórych badaniach raportowano, że 22% pacjentów z rakiem prącia było młodszych niż 40 lat, a 7% młodszych niż 30 lat.¹⁶

W USA zachorowalność na raka prącia różni się w zależności od rasy i pochodzenia etnicznego. Najwyższą zachorowalność odnotowuje się wśród białych Latynosów (1,01 na 100 000), następnie wśród rdzennych mieszkańców Alaski i Ameryki (0,77), Afroamerykanów (0,62) i białych nie-Latynosów (0,51).⁵ Co istotne, status społeczno-ekonomiczny ma znaczący wpływ na zachorowalność – w Anglii wskaźniki zachorowalności na raka prącia są o 52% wyższe w najbardziej niekorzystnej ekonomicznie grupie kwintylowej w porównaniu z najmniej niekorzystną (2013-2017).¹⁴

Czynniki ryzyka raka prącia

Zidentyfikowano wiele czynników ryzyka raka prącia, które można podzielić na kilka głównych kategorii:

Zakażenie HPV

Zakażenie wirusem brodawczaka ludzkiego (HPV) jest uznawane za główny czynnik ryzyka raka prącia. Szacuje się, że DNA HPV można zidentyfikować w około 40-50% przypadków inwazyjnego raka prącia.⁵¹⁷ Częstość występowania HPV różni się znacznie w zależności od podtypu histologicznego raka – w przeglądzie systematycznym 52 badań stwierdzono, że ogólna częstość występowania HPV w raku prącia wynosi 50,8%, przy czym najwyższą częstość odnotowano w raku bazaloidalnym (84%), następnie w raku brodawkowato-bazaloidalnym (75,7%) i rakach brodawkowatych (58,7%). Najczęstszym genotypem HPV był HPV-16 (68,3%), następnie genotyp HPV-6 niskiego ryzyka (8,1%).⁵

HPV integruje się z genomem gospodarza i manipuluje funkcjami komórkowymi poprzez onkoproteiny E6 i E7, które są kluczowe dla karcynogenezy indukowanej przez HPV. Wirusy te również indukują hipermetylację DNA genomu komórki gospodarza, selektywnie hamując geny supresorowe nowotworu na korzyść onkogenów.¹⁷

Brak obrzezania i stulejka

Stulejka (phimosis), czyli niemożność całkowitego odciągnięcia napletka, jest silnym czynnikiem ryzyka raka prącia. Stulejka występuje u około 25-75% pacjentów z rakiem prącia w największych seriach przypadków.¹⁸ W badaniach wykazano iloraz szans (OR) dla rozwoju raka prącia związanego ze stulejką w zakresie 4,9-7,2.⁸ Stulejka utrudnia odpowiednie oczyszczanie prącia, co może prowadzić do infekcji lub przewlekłego stanu zapalnego.¹⁹

Obrzezanie, szczególnie wykonane w okresie noworodkowym, ma silny efekt ochronny przed rakiem prącia. Przegląd systematyczny przeprowadzony przez Larke i wsp. wykazał silny ochronny wpływ wczesnego obrzezania na inwazyjnego raka prącia z ilorazem szans (OR) wynoszącym 0,33.⁸ Kraje o wysokich wskaźnikach obrzezania, takie jak Izrael, mają najniższą zachorowalność na świecie wynoszącą 0,1 na 100 000.¹⁶

Palenie tytoniu

Palenie tytoniu jest uznanym czynnikiem ryzyka raka prącia, ze wskazanym związkiem dawka-odpowiedź. Palacze konsumujący więcej niż 10 papierosów dziennie mieli znacznie wyższe ryzyko raka prącia w porównaniu do osób palących 1-10 papierosów dziennie.¹⁷ Badania wykazały, że palenie zwiększa ryzyko raka prącia 2,4-krotnie.²

Stan zapalny i schorzenia skórne

Przewlekły stan zapalny jest proponowanym mechanizmem karcynogenezy w wielu typach nowotworów złośliwych, w tym raka prącia. Meta-analiza 443 przypadków wykazała iloraz szans 3,82 dla rozwoju raka prącia związanego z zapaleniem żołędzi (balanitis).⁸

Liszaj twardzinowy (lichen sclerosus), przewlekła choroba zapalna, a także jej progresywny wariant znany jako balanitis xerotica obliterans (BXO), również zostały powiązane z rozwojem nowotworu. Od jednej trzeciej do połowy przypadków raka prącia jest związana z liszajem twardzinowym.²⁰

Inne czynniki ryzyka

Niski status społeczno-ekonomiczny i niski poziom wykształcenia – badanie populacyjne ze Szwecji wykazało zwiększone ryzyko inwazyjnego raka prącia u osób o niskim dochodzie do dyspozycji i niskim poziomie wykształcenia.⁸
Otyłość – raport Barnes i wsp. w populacji szpitalnej wykazał 49% zwiększone szanse rozpoznania inwazyjnego raka prącia na każde pięć jednostek wzrostu BMI u mężczyzn z nadwagą.⁸
Osłabiony układ odpornościowy (immunosupresja) zwiększa ryzyko raka prącia.¹⁹
Leczenie PUVA (psoralen + naświetlanie UVA) zostało powiązane z rakiem prącia.²¹
Wielokrotni partnerzy seksualni – rozpowszechnienie HPV jest dodatkowo zwiększone przez liczbę partnerów seksualnych, co jest kolejnym istotnym czynnikiem ryzyka raka prącia.¹⁷

Nadzór i strategie obserwacji w raku prącia

Rak prącia może wiązać się z wysokim ryzykiem nawrotu w regionalnych węzłach chłonnych i miejscach odległych. Strategie nadzoru ukierunkowane na wczesne wykrycie i leczenie są zalecane ze względu na znaczącą chorobowość i śmiertelność związaną z nawrotami.²²²³

Znaczenie wczesnego wykrywania nawrotów

Nawroty po pierwotnej terapii raka prącia mogą być wyleczalne, jeśli zostaną wcześnie wykryte, dlatego zalecana jest ścisła obserwacja.²² Lokalne lub regionalne nawroty w węzłach chłonnych zwykle występują w ciągu dwóch lat od leczenia pierwotnego.²⁴ Ryzyko nawrotu po pierwotnej terapii raka prącia zależy od stopnia i stadium zaawansowania. Dlatego odpowiednia dla stopnia i stadium strategia nadzoru jest konieczna u wszystkich pacjentów, w tym leczonych z zachowaniem narządu, takich jak zabiegi oszczędzające prącie (np. miejscowe wycięcie, glansektomia i dystalna korporektomia), ablacja laserowa, terapie miejscowe i radioterapia.²²

Zalecenia dotyczące obserwacji

Większość wytycznych, w tym Europejskiego Towarzystwa Urologicznego i National Comprehensive Cancer Network, zaleca wizyty kontrolne co 3 miesiące w pierwszych 2 latach, co 6 miesięcy w latach 3-5 i corocznie po tym okresie.²² Zaleca się długoterminową obserwację u wszystkich pacjentów, biorąc pod uwagę wysokie ryzyko nawrotu – czynnika prognostycznego złego przeżycia całkowitego.²²²³

Intensywność obserwacji zależy od patologicznego stadium i stopnia zaawansowania choroby oraz przeprowadzonego leczenia.²³ Zalecana jest dożywotnia obserwacja, ponieważ nawrót może wystąpić po ponad 5 latach.²³

Strategie nadzoru w zależności od ryzyka

Niezależnie od zastosowanego leczenia, w przypadku choroby wysokiego ryzyka (w porównaniu do choroby niskiego ryzyka) zalecany jest bardziej intensywny harmonogram nadzoru, dodając okresowe obrazowanie przekrojowe jako uzupełnienie badania fizykalnego.²²²³

U pacjentów z ujemnym wynikiem biopsji dynamicznej węzłów wartowniczych (DSNB) należy wdrożyć rygorystyczny harmonogram obserwacji, szczególnie w pierwszych 2 latach, ze względu na stosunkowo wysokie wskaźniki wyników fałszywie ujemnych.²³

Badanie kliniczne, wywiad i badanie fizykalne ukierunkowane na wczesne wykrycie nawrotowych zmian w miejscu leczonego guza pierwotnego lub gdzie indziej na prąciu powinny być wykonywane regularnie.²³

Centralizacja opieki i wyspecjalizowane ośrodki

Ze względu na rzadkość występowania raka prącia, powstaje potrzeba identyfikacji ośrodków referencyjnych specjalizujących się w leczeniu tego nowotworu. W jednym brytyjskim specjalistycznym ośrodku raka prącia (populacja referencyjna około 11 milionów) zaobserwowano poprawę 5-letnich wskaźników przeżycia swoistego dla raka (CSS) o nawet 12-85% po centralizacji.²⁴

Idealne byłoby kierowanie pacjentów po operacji węzłów chłonnych do specjalistycznych usług leczenia obrzęku limfatycznego w celu oceny i leczenia, zanim wystąpi znaczący obrzęk limfatyczny.²⁴

Przeżycie i wyniki leczenia

Wyniki pacjentów z rakiem prącia zależą od kilku czynników, w tym stadium klinicznego i cech histologicznych. Dane z 18 rejestrów nowotworów w Stanach Zjednoczonych wskazują na ogólne 5-letnie przeżycie względne wynoszące 67%, bez znaczących zmian w porównaniu 5-letnich okresów między 2000-2014.⁵

Przeżycie w zależności od stadium zaawansowania

Pacjenci z chorobą zlokalizowaną mają najlepsze rokowanie z 5-letnim przeżyciem względnym sięgającym 81%. Natomiast pacjenci z przerzutami odległymi mają najgorsze rokowanie z zaledwie 16% 5-letnim przeżyciem względnym.⁵

W Anglii przewiduje się, że ponad dwie trzecie (68%) mężczyzn zdiagnozowanych z rakiem prącia przeżywa swoją chorobę przez dziesięć lub więcej lat (2009-2013).¹⁵

Według danych National Cancer Institute SEER, u 37% pacjentów z rakiem płaskonabłonkowym prącia zdiagnozowano raka in situ (CIS), u 39% chorobę zlokalizowaną, u 13% chorobę regionalną, u 2,3% chorobę przerzutową, a u 7,9% chorobę niesklasyfikowaną. Średni czas do zgonu z powodu raka wynosił 66,8 miesiąca u osób z CIS, 50,1 miesiąca u osób z chorobą zlokalizowaną, 32,4 miesiąca u osób z chorobą regionalną i 7,4 miesiąca u osób z przerzutami odległymi.¹⁶

Znaczenie zajęcia węzłów chłonnych

Obecność i stopień zajęcia regionalnych węzłów chłonnych pachwinowych jest najważniejszym pojedynczym wskaźnikiem prognostycznym w określaniu długoterminowego przeżycia u mężczyzn z inwazyjnym rakiem płaskonabłonkowym prącia.²⁵ W dużym retrospektywnym przeglądzie 700 pacjentów stwierdzono, że terapie oszczędzające prącie wiążą się ze znacznie wyższym ryzykiem nawrotu miejscowego (28%) niż częściowa lub całkowita penektomia (5%), a zatem wymagają ściślejszego nadzoru.²⁵

Pacjenci bez zajęcia węzłów chłonnych mieli częstość nawrotów regionalnych wynoszącą 2% w porównaniu z 19% dla pacjentów z chorobą N+.²⁵

Czynniki prognostyczne

Główne czynniki prognostyczne istotnie wpływające na przeżycie pacjentów z rakiem prącia to:

Obecność i stopień przerzutów do węzłów chłonnych²⁵
Stadium histopatologiczne i stopień zróżnicowania guza¹¹
Obecność przerzutów w momencie diagnozy¹⁸
Dodatni status HIV¹⁸
Wysoka ekspresja ki-67 i p53¹¹
Inwazja naczyń limfatycznych i okołonerwowa¹¹

Profilaktyka i wczesne wykrywanie

Biorąc pod uwagę zidentyfikowane czynniki ryzyka, istnieje kilka strategii, które mogą zmniejszyć ryzyko rozwoju raka prącia:²¹²⁶

Obrzezanie noworodkowe – znacznie zmniejsza ryzyko raka prącia⁸
Ograniczenie zakażeń HPV – poprzez szczepienia profilaktyczne lub stosowanie prezerwatyw²¹
Zapobieganie stulejce – poprzez edukację lekarzy i rodziców o znaczeniu nieingerencji w fizjologiczny proces oddzielania napletka u małych chłopców²⁶
Leczenie przewlekłych stanów zapalnych²¹
Ograniczenie leczenia PUVA²¹
Zaprzestanie palenia²⁷
Poprawa higieny²¹

Szczepienia przeciwko HPV są szczególnie obiecującą strategią profilaktyczną. Ponieważ do 50% inwazyjnych raków prącia i 80% zmian przednowotworowych jest związanych z HPV, zachęca się do szczepień przeciwko HPV.⁵ Obecnie w USA szczepienia przeciwko HPV są zatwierdzone dla mężczyzn w wieku 9-26 lat w celu zapobiegania brodawkom narządów płciowych i rakowi odbytu.²⁸

Poprawa higieny prącia i promowanie powszechnego stosowania szczepionek przeciwko HPV dla mężczyzn powinny być częścią programów profilaktyki raka prącia w przyszłości.³ Kampanie zdrowia publicznego są potrzebne w krajach rozwijających się, aby skoncentrować się na zwiększeniu wskaźników obrzezania noworodków, zwalczaniu tendencji do palenia, promowaniu lepszej higieny i dążeniu do szerokiego wdrożenia szczepionki przeciwko HPV.⁸

Świadomość społeczna i edukacja pacjentów są istotne i mogą być przekazywane przez szkoły, media społecznościowe, magazyny męskie, billboardy i kampanie uświadamiające prowadzone przez organizacje charytatywne.²⁹

Wyzwania w diagnostyce i leczeniu

Diagnostyka raka prącia pozostaje wyzwaniem ze względu na jego rzadkość i różnorodność prezentacji klinicznych.¹⁷³⁰ Opóźnienie w diagnozie raka prącia jest dobrze udokumentowane.³¹

Ze względu na rzadkość tego nowotworu w Stanach Zjednoczonych, badania kliniczne specyficzne dla raka prącia są rzadkie.⁷ Pacjenci z chorobą w stadium III i IV są kandydatami do badań klinicznych fazy I i II testujących nowe leki, terapie biologiczne lub techniki chirurgiczne w celu poprawy kontroli miejscowej i przerzutów odległych.⁷

Wpływ HPV na mikrośrodowisko immunologiczne guza komplikuje postępowanie kliniczne, chociaż ostatnie postępy w inhibitorach punktów kontrolnych układu odpornościowego (ICI) wykazały pewną skuteczność w leczeniu raka prącia związanego z HPV.¹⁷³⁰

Leczenie raka prącia w krajach o ograniczonych zasobach, takich jak Tanzania, stwarza poważne wyzwania diagnostyczne i terapeutyczne, które muszą zostać rozwiązane. Większość pacjentów zgłasza się późno z zaawansowanym stadium choroby.¹⁸

Właściwą opieką medyczną po zakończeniu leczenia byłoby kierowanie pacjentów po operacji węzłów chłonnych do specjalistycznych usług leczenia obrzęku limfatycznego w celu oceny i leczenia, zanim wystąpi znaczący obrzęk limfatyczny.²⁴ Dostęp do wsparcia psychologicznego, poradnictwa i terapii psychoseksualnej to kluczowe elementy holistycznej i wielodyscyplinarnej usługi wsparcia pacjentów.²⁴

Rak prącia ma znaczący wpływ na jakość życia na wiele sposobów i wciąż istnieje wiele niezaspokojonych potrzeb do rozwiązania. Istnieje bardzo mało danych na temat jakości życia po leczeniu raka prącia. W szczególności istnieje heterogeniczność narzędzi psychometrycznych używanych do oceny wyników jakości życia i potrzebne są dalsze badania w celu opracowania specyficznych dla choroby PROMS (Patient-Reported Outcome Measures) dla raka prącia.²⁴

Kolejne rozdziały

Zapraszamy do dalszego czytania naszego leksykonu.

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

Materiały źródłowe

#1 The Epidemiology of Penile Cancer – Urologic Cancers – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK585980/
Penile cancer is an uncommon type of malignancy. In 2020, globally, 36068 new cases were diagnosed according to the International Agency for Research on Cancer. The majority (over 95%) of penile cancers are squamous cell carcinoma. Penile cancer generally affects men from low socio-economic groups with poor hygienic standards. The highest figures have been recorded in countries such as South America, Africa, and India. Human papilloma virus (HPV16-18) infection, phimosis, and smoking have been found to be the strongest risk factors for penile cancer, and they can significantly increase its incidence. Penile cancer usually affects patients late in life, with the highest incidence recorded in the 60-year age group. […] Penile cancer is a rare tumor. With 36068 cases, it occupies 30th position on the list of the most common cancers recorded worldwide. The vast majority (over 95%) of penile cancer are squamous cell carcinoma. The most common are Grade 12 tumors. Penile cancer is typical of non-industrialized countries with low hygiene and education standards. Its incidence varies greatly from country-to-country. The highest rates are reported in South America, South Africa, and India. The incidence increases with age, being the highest in the 60 year age group. This chapter provides an overview of the global incidence and risk factors of penile cancer.
#2 The Epidemiology of Penile Cancer – Urologic Cancers – NCBI Bookshelf
https://www.ncbi.nlm.nih.gov/books/NBK585980/
Several risk factors, such as Phimosis, human papilloma virus (HPV), smoking, and low social economic status have been found to associated to penile cancer. […] Penile cancer is a rare cancer. With 36,068 cases and 13,211 deaths in 2020, it occupies the 30th position for incidence and the 31st place for number of deaths among all cancer. Its age standardized rate per 100,000 inhabitants (ASR) is around 0.8 and vary greatly around the globe. Penile cancer generally affects populations from developing countries such as South America, South Africa, and South-Central Asia. […] Penile cancer is a rare malignancy. With 36068 cases recorded in 2020, it occupies the 30th position of the commonest cancers and the 31st per mortality. Over 95% of penile cancer diagnosed are squamous cell carcinoma type, and the majority are Grade 1 and 2. It has been observed that penile cancer is more common in non- or low-industrialized countries, in particular in those where hygienic standards and income are the lowest. South America, Africa, and India are the area where the incident is the highest. The population affected is generally old, with the highest figures recorded in the over 60-year age groups. Multiple risks factors have been identified with HPV infection as strongest factor. It is believed that over 50% of the penile cancer are attributable to HPV, and of these, 73% caused by the HPV 16/18 strains. Phimosis and smoking increase the risk of penile cancer 11.4 and 2.4 times, respectively. Strong emphasis will have to be given to prevention, awareness, and HPV vaccination programs.
#3 JMIR Public Health and Surveillance – Global Pattern and Trends in Penile Cancer Incidence: Population-Based Study
https://publichealth.jmir.org/2022/7/e34874
Background: Penile cancer is a relatively rare genital malignancy whose incidence and mortality are rising in many countries. […] The estimated age-standardized incidence of penile cancer worldwide was 0.80 per 100,000 person-years in 2018, and the incidence is predicted to increase by more than 56% by 2040, according to the Global Cancer Registries (GLOBOCAN) Cancer Tomorrow prediction tool. […] The incidence of penile cancer has been increasing in many areas in the past few decades. […] We aimed to examine the geographical variations in incidence and mortality patterns of penile cancer among 185 countries in 2020 and the long-term incidence trends in 43 countries with 44 populations during the period between 1973 and 2012. […] The global estimated ASIR of penile cancer was 0.8 (per 100,000) in 2020, with estimates indicating 36,068 newly diagnosed cases.
#3 JMIR Public Health and Surveillance – Global Pattern and Trends in Penile Cancer Incidence: Population-Based Study
https://publichealth.jmir.org/2022/7/e34874
Both ASIR and ASMR in low- and middle-income countries were nearly twice as those in high-income countries. […] The trends in the ASIR of penile cancer between one year and another in 44 populations from 43 countries are displayed. […] We found that the higher incidence and mortality of penile cancer remain centered in developing settings, such as Southern Africa, South Asia, and South America. […] We found a significantly increasing trend in the ASIR of penile cancer among most European countries during the study period, especially in Northern Europe. […] The incidence trend of penile cancer observed in this study is similar to other long-lag HPV-related cancers, such as vulvar cancer and anal cancer. […] While the higher incidence and mortality of penile cancer remain in some developing countries, these have significantly increased in most European populations studied, but have also decreased in a few countries. […] Improving penile hygiene and promoting the widespread use of male HPV vaccines should be part of prevention programs for penile cancer in the future.
#4
https://exonpublications.com/index.php/exon/article/view/epidemiology-of-penile-cancer
Penile cancer is an uncommon type of malignancy. In 2020, globally, 36068 new cases were diagnosed according to the International Agency for Research on Cancer. […] The majority (over 95%) of penile cancers are squamous cell carcinoma. Penile cancer generally affects men from low socio-economic groups with poor hygienic standards. […] The highest figures have been recorded in countries such as South America, Africa, and India. Human papilloma virus (HPV16-18) infection, phimosis, and smoking have been found to be the strongest risk factors for penile cancer, and they can significantly increase its incidence. […] Penile cancer usually affects patients late in life, with the highest incidence recorded in the 60-year age group.
#5 EAU Guidelines on Penile Cancer – Uroweb
https://uroweb.org/guidelines/penile-cancer/chapter/epidemiology-aetiology-and-pathology
More than 95% of penile cancers are SCCs. Penile cancer incidence varies across the world. In industrialised countries, penile cancer is uncommon, with an overall incidence of around 0.94/100,000 males in Europe and 0.5 in the USA. In contrast, in South America, Southeast Asia and parts of Africa, the incidence is much higher and can account for 12% of malignant disease in men. The annual age-adjusted incidence is 0.73.0 in India, 8.3 in Brazil (per 100,000, respectively) and is higher in parts of Africa such as Uganda. In Europe, there is considerable variation across countries. Data from Norway showed an increase in the age-standardised incidence rates in 5-year periods from 2001-2015 compared to the previous periods (0.65/100,000 in 195660 vs. 0.91/100,000, in 2011-2015) with an Estimated Annual Percent Change of +0.80%. In the United Kingdom, the age-standardised incidence rate increased 28% between 1993 and 2018. This trend was seen in age groups from 5079 years old. Incidence rates remained unchanged for both age extremes ( 50 and 79 years). Based on 16 cancer registries in France, incidence rates between 2009 and 2011 were 0.59 per 100,000 men (95% CI: 0.500.68) and these rates have remained stable since 1989. In the USA, the incidence of penile cancer is affected by race and ethnicity, with the highest incidence in white Hispanics (1.01), followed by Alaskans and Native American Indians (0.77), African Americans (0.62) and white non-Hispanics (0.51), per 100,000 males, respectively. The overall age-adjusted incidence rate decreased between 1973 and 2002; per decade from 0.84 (19731982), to 0.69 (19831992), and 0.58 (19932002) per 100,000 males, respectively. An increasing trend, slightly surpassing the previous incidence rates, was described using the Surveillance, Epidemiology and End Result (SEER) 20002016 data, showing an estimated annual percent change of +3.5% from 2004-2016. The incidence increases with age, with a peak in the sixth decade but it does occur in younger men. Penile cancer is common in regions with a high prevalence of human papillomavirus (HPV), and approximately one-third to half of cancer cases are attributed to HPV-associated carcinogenesis. In summary, it seems that a slight increase in incidence is seen in Western/developed countries, most likely caused by higher infection rates of HPV which is a trend also observed in oropharynx carcinoma. Several risk factors for penile cancer have been identified, such as phimosis, chronic penile inflammation, lichen sclerosus, smoking, ultraviolet A phototherapy, and low socio-economic status, amongst others. Patient outcome is influenced by clinical and histologic features. United States SEER data from 18 cancer registries indicated an overall 5-year relative survival of 67% with no significant changes when comparing 5-year spans between 20002014. Patients with localised disease showed the best outcome with up to 81% 5-year relative survival. Patients with distant metastases have the worst outcomes with only 16% 5-year relative survival. Human papilloma virus infection is the main risk factor for penile cancer. Human papilloma virus deoxyribonucleic acid (DNA) has been identified in intraepithelial neoplasia and invasive penile cancer tissue samples. The HPV virus interacts with oncogenes and tumour suppressor genes (p16, P53, Rb genes). The rate of HPV-positivity differs between different histological subtypes of penile SCC. Human papilloma virus is a co-factor in the carcinogenesis of some subtypes of penile SCC, while others are not related to HPV. The risk of penile cancer is increased in patients with condyloma acuminata. A SR of 52 studies concluded that the overall HPV prevalence in penile cancer is 50.8%. Among HPV-associated carcinomas, basaloid carcinoma showed the highest prevalence (84%) followed by warty-basaloid carcinoma (75.7%) and warty carcinomas (58.7%). In histologically HPV-independent carcinomas, HPV prevalence was 19.4%. The most frequent HPV genotypes were HPV16 (68.3%), followed by the low-risk HPV6 genotype (8.1%). At present, except in a limited number of countries, there is no general recommendation for HPV vaccination in males because of the different HPV-associated risk patterns in penile- and cervical cancer. Since up to 50% of invasive penile carcinomas and 80% of pre-neoplastic lesions are HPV-associated, HPV vaccination is encouraged. Phimosis is strongly associated with invasive penile cancer, due to associated chronic infections. However, smegma is not a carcinogen. The incidence of lichen sclerosus is relatively high in penile cancer patients but is not associated with adverse histopathological features, including penile intraepithelial neoplasia (PeIN). Other epidemiological risk factors are cigarette smoking, low socio-economic status, and a low level of education. Neonatal circumcision reduces the incidence of penile cancer; however, it does not seem to reduce the risk of PeIN. The lowest incidence of penile cancer is reported in Israeli Jews (0.3/100,000/year).
#6 Key Statistics for Penile Cancer | American Cancer Society
https://www.cancer.org/cancer/types/penile-cancer/about/key-statistics.html
The American Cancer Society estimates for penile cancer in the United States for 2025 are: […] About 2,190 new cases of penile cancer diagnosed […] About 510 deaths from penile cancer. […] Penile cancer is rare in North America and Europe. It’s diagnosed in fewer than 1 man in 100,000 each year and accounts for fewer than 1% of cancers in men in the United States. Penile cancer is much more common in some parts of Asia, Africa, and South America.
#7 Penile Cancer Treatment (PDQÂ®) – NCI
https://www.cancer.gov/types/penile/hp/penile-treatment-pdq
Estimated new cases and deaths from penile (and other male genital) cancer in the United States in 2025: […] New cases: 2,190. […] Deaths: 510. […] Penile cancer is rare in most developed nations, including the United States, where the incidence rate is less than 1 per 100,000 men per year. […] Some studies suggest an association between human papillomavirus (HPV) infection and penile cancer. […] Observational studies have shown a lower prevalence of penile HPV in men who have been circumcised (odds ratio, 0.37; 95% confidence interval, 0.160.85). […] Some, but not all, observational studies also suggest that male newborn circumcision is associated with a decreased risk of penile cancer. […] According to published data, if the relationship is causal, the number needed to treat was about 909 circumcisions to prevent a single case of invasive penile cancer.
#7 Penile Cancer Treatment (PDQÂ®) – NCI
https://www.cancer.gov/types/penile/hp/penile-treatment-pdq
When diagnosed early (stage 0, stage I, and stage II), penile cancer is highly curable. […] Curability decreases sharply for stage III and stage IV disease. […] Because of the rarity of this cancer in the United States, clinical trials specifically for penile cancer are infrequent. […] Patients with stage III and stage IV cancer are candidates for phase I and phase II clinical trials testing new drugs, biological therapy, or surgical techniques to improve local control and distant metastases. […] The selection of treatment depends on the following tumor characteristics: Size, Location, Invasiveness, Stage. […] Stage 0 penile cancer is defined by the following TNM classifications: Tis, N0, M0; Ta, N0, M0. […] Carcinoma in situ of the penis is referred to as erythroplasia of Queyrat when it occurs on the glans, and Bowen disease when it occurs on the penile shaft.
#8 Updates on the epidemiology and risk factors for penile cancer – Douglawi – Translational Andrology and Urology
https://tau.amegroups.org/article/view/15046/html
In contrast, the incidence is significantly higher in developing countries where penile cancer constitutes a significant public health hazard. […] Countries that suffer from economic disparity or have low rates of circumcision such as Brazil, India and African nations, have the highest reported incidence with rates as high as 6% of malignant neoplasms. […] Conversely, countries with robust medical systems and religious practices leading to high rates of circumcision, such as Israel, report the lowest incidence at 0.1 in 100,000. […] Penile cancer is a fairly rare diagnosis in developed nations. […] The incidence in Europe and the United Kingdom are similar to USA with rates ranging between 0.45-1.7 per 100,000, however, while incidence in Europe and the USA has been on a decline, a recent article reported an increase in incidence in the UK from 1.1 to 1.33 in 100,000 men between 1979 and 2009.
#8 Updates on the epidemiology and risk factors for penile cancer – Douglawi – Translational Andrology and Urology
https://tau.amegroups.org/article/view/15046/html
Numerous risk factors have been shown to increase the risk of developing invasive disease. […] The lack of circumcision is a well-accepted risk factor for penile cancer. […] The protective effect of circumcision was first reported in 1932 in a large cohort study of penile cancer patients that revealed a stark demographic anomaly, as there were zero cases in the Jewish patients. […] A recent systematic review by Larke et al. found a strong protective effect of early circumcision on invasive penile cancer with an odds ratio (OR) of 0.33. […] Phimosis is a potent risk factor for penile cancer with OR range of 4.9-7.2 and likely facilitates the increased risk seen with lack of circumcision. […] Chronic inflammation is a proposed mechanism for carcinogenesis in multiple types of malignancies.
#8 Updates on the epidemiology and risk factors for penile cancer – Douglawi – Translational Andrology and Urology
https://tau.amegroups.org/article/view/15046/html
A meta-analysis of 443 cases found a OR of 3.82 for developing penile cancer associated with balanitis. […] Lichen sclerosis, a chronic inflammatory condition, as well as a progressive variant known as balanitis xerotica obliterans (BXO), have also been implicated in development of malignancy. […] Obesity is a well-recognized risk factor for malignancies in general with a reported population attributable factor of 3.6% for all malignancies. […] A report by Barnes et al. in a hospital based population showed a 49% increased odds of invasive penile cancer diagnosis for every five-unit increase in BMI in overweight men. […] Socioeconomic disparities are associated with increased cancer incidence in general. […] A population based study from Sweden reported increased risk of invasive penile cancer in those with low disposable income and low education level.
#8 Updates on the epidemiology and risk factors for penile cancer – Douglawi – Translational Andrology and Urology
https://tau.amegroups.org/article/view/15046/html
Premalignant lesions are benign entities that are thought to have the potential for malignant transformation. […] The immune system has a significant influence on the risk for contracting HPV as well as its infectious course and clearance, which affects the development of some premalignant lesions. […] Smoking has been implicated as a risk factor for multiple malignancy sites and penile cancer is no exception. […] There has been a great deal of emphasis on HPVs potential for carcinogenesis in the past few years. […] While penile cancer is quite rare in developed countries, it continues to be a significant public health issue in developing nations. […] Public health campaigns are needed in developing countries to focus on increasing neonatal circumcision rates, combatting smoking trends, promoting better hygiene, and pursuing wide deployment of the HPV vaccine.
#9 Profile of patients with penile cancer in the region with the highest worldwide incidence | Scientific Reports
https://www.nature.com/articles/s41598-020-59831-5
To determine the epidemiological, histopathological, and clinical characteristics of patients diagnosed with penile cancer in the Brazilian state of Maranho, the region with the highest incidence worldwide. […] Brazil has a high incidence, and the state of Maranho, located in the northeastern region of the country, has the highest incidence of penile cancer in the world (ASR of 6.1 cases per 100,000 inhabitants). […] The population with penile cancer in the region of highest incidence in the world is marked by low socioeconomic status, high prevalence of HPV infection, and phimosis. […] The high prevalence of young patients was also a striking feature. […] The population with penile cancer in the region with the highest worldwide incidence is marked by a high prevalence of HPV infection and phimosis. Together with the low socioeconomic level of the patients, these are leading factors for the development of the neoplasm. A delay in seeking treatment was related to the high frequency of advanced tumors and aggressive surgical treatment.
#10 Penile cancer – Wikipedia
https://en.wikipedia.org/wiki/Penile_cancer
Penile cancer is a rare cancer in developed nations, with annual incidence varying from 0.3 to 1 per 100,000 per year, accounting for around 0.4-0.6% of all malignancies. The annual incidence is approximately 1 in 100,000 men in the United States, 1 in 250,000 in Australia, and 0.82 per 100,000 in Denmark. In the United Kingdom, fewer than 500 men are diagnosed with penile cancer every year. […] In the developing world, penile cancer is much more common. For instance, in Paraguay, Uruguay, Uganda and Brazil the incidence is 4.2, 4.4, 2.8 and 1.5-3.7 per 100,000, respectively. In some South American countries, Africa, and Asia, this cancer type constitutes up to 10% of malignant diseases in men. […] As of 1997 the lifetime risk was estimated as 1 in 1,437 in the United States and 1 in 1,694 in Denmark.
#11 A comprehensive analysis of penile cancer in the region with the highest worldwide incidence reveals new insights into the disease | BMC Cancer | Full Text
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-10127-z
Although penile cancer (PC) is uncommon in developed countries, it is widespread in developing countries. The state of Maranho (Northeast, Brazil) has the highest global incidence recorded for PC, and, despite its socioeconomic vulnerability, it has been attributed to human papillomavirus (HPV) infection. […] Our data reaffirmed the high incidence of HPV infection in PC cases from Maranho and offer new insights into potential factors that may contribute to the high PC incidence in the region. We highlighted the possible association of HPV with worse clinical prognosis factors, differently from what was observed in other regions. […] The disease appears to be more prevalent in older men living in rural zones and those with low education levels. PC has been linked to smoking, alcoholism, phimosis, obesity, poor hygiene of the penis, chronic inflammatory conditions, and human papillomavirus (HPV) infection.
#11 A comprehensive analysis of penile cancer in the region with the highest worldwide incidence reveals new insights into the disease | BMC Cancer | Full Text
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-10127-z
Since the prevalence of PC appears to vary considerably between certain regions of Brazil, local studies are essential to better understand the reality of PC in the country. […] In northeastern Brazil, the state of Maranho has attracted the attention of the scientific community owing to its high prevalence of PC. […] Our research group and others have aimed to better understand PC features in Maranho. Over the past five years, these studies have drawn attention to a clinical, epidemiological, and etiological profile distinct from that observed in other studies carried out in Brazil and worldwide, with marked heterogeneity of histological subtypes and high prevalence of HPV infection. […] We found a significant impact of high ki-67 and p53 expression on decreasing patients survival, as well as grade, pT, stage, pattern, and depth of invasion.
#11 A comprehensive analysis of penile cancer in the region with the highest worldwide incidence reveals new insights into the disease | BMC Cancer | Full Text
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-10127-z
HPV positivity was associated with tumors located in the glans and the presence of carcinoma in situ associated, while the absence of HPV was associated with tumors in advanced stages. […] The high prevalence of HPV-positive tumors reported in the last five years has been one of the most notable findings in Maranho. […] The presence of koilocytosis was associated with men reporting more than 10 lifetime sexual partners, tumors with HPV-associated histology, and warty subtype. […] The association between high ki-67 expression and angiolymphatic and perineural invasion is another important finding of our study and was previously described for PC.
#12 Epidemiology, Diagnosis and Management of Penile Cancer: Results from the Spanish National Registry of Penile Cancer
https://www.mdpi.com/2072-6694/15/3/616
Epidemiology, Diagnosis and Management of Penile Cancer: Results from the Spanish National Registry of Penile Cancer […] Penile cancer is a rare malignant tumor mainly affecting adult/older men. Given the rarity of this disease, affecting 1/100,000 men every year, risk factors and diagnostic procedures are often inadequately described. This is the first multicenter study to describe the approach to this disease in Spain. The results highlight the need for the institution of referral centers and standardized diagnostic pathways for the optimal management of this disease. […] Penile cancer (PC) is a rare malignancy with an overall incidence in Europe of 1/100,000 males/year. In Europe, few studies report the epidemiology, risk factors, clinical presentation, and treatment of PC. The aim of this study is to present an updated outlook on the aforementioned factors of PC in Spain. The incidence of PC in Spain in 2015 was 2.55/100,000 males per year. A total of 586 patients were identified, and 228 patients from 61 hospitals were included in the analysis. A total of 54/61 (88.5%) centers reported â¤ 5 new cases. The patients accessed the urologist for visually-assessed penile lesions (60.5%), mainly localized in the glans (63.6%). Local hygiene, smoking habits, sexual habits, HPV exposure, and history of penile lesions were reported in 48.2%, 59.6%, 25%, 13.2%, and 69.7%. HPV-positive lesions were 18.1% (28.6% HPV-16). The majority of PC was squamous carcinoma (95.2%). PC was â¥cT2 in 45.2% (103/228) cases. At final pathology, PC was â¥pT2 in 51% of patients and â¥pN1 in 17% of cases. The most common local treatment was partial penectomy (46.9% cases). A total of 47/55 (85.5%) inguinal lymphadenectomies were open. Patients with â¥pN1 disease were treated with chemotherapy in 12/39 (40.8%) of cases. […] PC incidence is relatively high in Spain compared to other European countries. The risk factors for PC are usually misreported. The diagnosis and management of PC are suboptimal, encouraging the identification of referral centers for PC management.
#13 The Burden of Penile Cancer in Bali Compared to Other Provinces in Indonesia | Open Access Macedonian Journal of Medical Sciences Open Access Macedonian Journal of Medical Sciences (OAMJMS).
https://oamjms.eu/index.php/mjms/article/view/7472
Objective: In Indonesia, 45% of the total penile cancer cases are concentrated in Bali province, where penile cancer is ranked as the most common cancer during 2013. However, the incidences of penile cancer in Bali and other provinces in Indonesia are still unknown. The purpose of this study is to determine the age-standardized incidence rate (ASR), age-specific incidence rate (AR), and crude rate incidence (CRI) of penile cancer in Bali and other provinces in Indonesia. […] Result: There were variations on ASR, AR, and CRI for penile cancer in Indonesia. We found that the average CRI in Indonesia is 0.1 per 100,000 men. The incidence is found to be higher in Bali compared to other provinces. The average ASR in Bali is 2.1 per 100,000 men, CRI is 2.5 per 100,000 men, and the peak of AR being 12.9 per 100,000 men in the age group of 55-64 years old. The incidence of penile cancer is found to increase with age. In Bali, the peak incidence is in the 6th and 7th decades of life. The ASR and CRI of penile cancer in other provinces were less than 1 per 100,000 males. […] Conclusion: The highest incidence of penile cancer is found in the Bali province compared to other provinces in Indonesia. This problem requires more serious attention and further research to identify the risk factors.
#14 Penile cancer incidence statistics | Cancer Research UK
https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/penile-cancer/incidence
Penile cancer European age-standardised (AS) incidence rates for males increased by 37% in the UK between 1993-1995 and 2017-2019. […] Over the last decade in the UK (between 2007-2009 and 2017-2019), penile cancer AS incidence rates for males increased by 25%. […] Penile cancer incidence rates have varied between age groups in males in the UK since the early 1990s. […] For penile cancer, like most cancer types, incidence trends largely reflect changing prevalence of risk factors and improvements in diagnosis and data recording. Recent incidence trends are influenced by risk factor prevalence in years past, and trends by age group reflect risk factor exposure in birth cohorts. […] Penile cancer incidence rates (European age-standardised (AS) rates) in England in males are 52% higher in the most deprived quintile compared with the least (2013-2017).
#14 Penile cancer incidence statistics | Cancer Research UK
https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/penile-cancer/incidence
Penile cancer is not among the 20 most common cancers in males in the UK, accounting for less than 1% of all new cancer cases in males (2017-2019). In females and males combined, penile cancer is not among the 20 most common cancers in the UK, accounting for less than 1% of all new cancer cases (2017-2019). […] Penile cancer incidence rates (European age-standardised (AS) rate) for males are similar to the UK average in all the UK constituent countries. […] In the UK in 2017-2019, on average each year around a third of new cases (32%) were in males aged 75 and over. […] Age-specific incidence rates rise steadily from around age 25-29, more steeply from age 40-44 and continue increasing with age. The highest rates are in the 90+ age group. […] For penile cancer, like most cancer types, incidence increases with age. This largely reflects cell DNA damage accumulating over time. Damage can result from biological processes or from exposure to risk factors.
#15 Penile cancer statistics | Cancer Research UK
https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/penile-cancer
There are around 760 new penile cancer cases in the UK every year, that’s around 2 every day (2017-2019). […] Penile cancer accounts for less than 1% of all new cancer cases in males in the UK (2017-2019). […] Penile cancer incidence rates are projected to rise by 9% in the UK between 2023-2025 and 2038-2040. […] There could be around 1,100 new cases of penile cancer every year in the UK by 2038-2040, projections suggest. […] Penile cancer is the not among the 20 most common causes of cancer death in males in the UK, accounting for less than 1% of all cancer deaths in males in the UK (2017-2019). […] Mortality rates for penile cancer in the UK are highest in males aged 90+ (2017-2019). […] Since the early 1970s, penile cancer mortality rates have decreased by almost a quarter (23%) in males in the UK (2017-2019).
#15 Penile cancer statistics | Cancer Research UK
https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/penile-cancer
Penile cancer mortality rates are projected to rise by 20% in the UK between 2023-2025 and 2038-2040. […] More than two-thirds (68%) of men diagnosed with penile cancer in England survive their disease for ten years or more, it is predicted (2009-2013). […] 63% of penile cancer cases in the UK are preventable.
#16 Penile Cancer: Practice Essentials, History of the Procedure, Problem
https://emedicine.medscape.com/article/446554-overview
Penile cancer tends to be a disease of older men. The incidence of penile cancer increases abruptly in men aged 60 years or older and peaks in men aged 80 years. However, the tumor is not unusual in younger men. One study reported that 22% of patients with penile cancer were younger than 40 years, and 7% were younger than 30 years. […] The National Cancer Institutes SEER program was used to gather data on 1605 men diagnosed with squamous cell carcinoma of the penis. Carcinoma in situ (CIS) was diagnosed in 37% of this population, localized disease was diagnosed in 39%, regional disease was present in 13%, distant disease was present in 2.3%, and unstaged disease remained in 7.9%. […] According to SEER data, the proportion of men presenting annually with CIS has tended to increase, although the number of men with localized disease has decreased. Older age at diagnosis was associated with a higher stage of disease. The mean time until death from cancer was 66.8 months in those with CIS, 50.1 months in those with localized disease, 32.4 months in those with regional disease, and 7.4 months in those with distant metastases. Overall, 22.4% of the patients in this database died of this cancer.
#16 Penile Cancer: Practice Essentials, History of the Procedure, Problem
https://emedicine.medscape.com/article/446554-overview
In contrast, a review of the National Cancer Database found that from 1998 to 2012, cases of all stages of penile squamous cell carcinoma increased, with a greater proportion of advanced cases over time. Factors significantly associated with advanced presentation were age older than 55 years, the presence of comorbidities, and Medicaid or no insurance. […] Penile cancer accounts for 0.4-0.6% of all malignancies in the United States and Europe. In the rest of the world, the situation is different and represents an important health problem. Penile carcinoma represents up to 10% of all cancers diagnosed in men in some parts of Asia, Africa, and South America. […] Penile cancer is rare in circumcised men, particularly if they were circumcised as a neonate. Worldwide, the lowest incidence rates of penile cancer, 0.1 cases per 100,000 men, are found in countries that have robust medical systems and religious practices leading to high rates of neonatal circumcision, such as Israel.
#17 HPV and Penile Cancer: Epidemiology, Risk Factors, and Clinical Insights
https://www.mdpi.com/2076-0817/13/9/809
The estimated age-standardized incidence rate (ASR) of PC in 2020 was 0.8 per 100,000 globally, with higher rates in South America, Southern Africa, and South Asia, where incidence can account for up to 10% of malignancies. In the United States, the incidence of PC is 0.38 per 100,000 with a mean age of 67. Most penile cancers are of squamous cell origin with frequent association with the human papillomavirus (HPV). Consequently, penile squamous cell carcinoma (PSCC) is generally classified as being either HPV-associated or HPV-independent. Other risk factors include phimosis, tobacco use, poor hygiene, sexual promiscuity, and a low socioeconomic status. HPV-associated penile cancers account for 38.5% of cases, with the HPV 16 serotype being the most common. […] The prevalence and incidence of penile cancer have varying trends globally. PC represents 1% of all malignancies in US men and 0.1% of all deaths related to malignancies. Historically, incidence rates in the US have been decreasing since the 1970s and have stabilized to 0.38 per 100,000 from 2000 to 2018. The 5-year relative survival rate has also remained consistent in the US from 2000 to 2014, ranging from 65.67% to 67.70%. Racial differences in incidence were also observed from 1995 to 2003, where Hispanic men had the greatest incidence and Asian Pacific Islanders had the lowest incidence.
#17 HPV and Penile Cancer: Epidemiology, Risk Factors, and Clinical Insights
https://www.mdpi.com/2076-0817/13/9/809
The pathophysiology of HPV-associated penile cancer is better understood than that of HPV-independent penile cancer. HR-HPV 16 binds to Heparan Sulfate Proteoglycans (HSPGs) and undergoes conformation changes to initiate early virusâhost cell interactions. The E6 and E7 oncoproteins are crucial for HPV-induced carcinogenesis. HPV-induced DNA hypermethylation of the host cell genome is another method the virus uses to selectively repress tumor suppressor genes in favor of oncogenes. […] HPV is a non-enveloped, circular, double-stranded DNA virus that enters the epithelium through the skin and mucosa to eventually infect the proliferating basal layer of keratinocytes. The transmission of HPV primarily occurs through sexual intercourse, with each sexual encounter presenting a 40% probability of HPV transfer. Following transmission, the HPV genome typically persists as extrachromosomal DNA in host cells. Over time, in some cases, the HPV genome integrates into host cells to influence the host cell genome, manipulate cellular functions, and contribute to a tumorigenic transformation.
#17 HPV and Penile Cancer: Epidemiology, Risk Factors, and Clinical Insights
https://www.mdpi.com/2076-0817/13/9/809
In India, PC has an incidence rate of up to 3.32 per 100,000, while Northeast Brazil has the highest incidence globally at an ASR of 6.1 per 100,000. A meta-analysis accumulating data from 1995 to 2022 found that the global pooled prevalence of HPV in men was 31%, with 21% being high-risk HPV. The prevalence varies between developing and developed countries; however, there is no indication that HPV-associated penile cancer is more prevalent in developing countries. In PC, there is a 50.8% prevalence of HPV DNA. […] Phimosis, the inability to retract the foreskin covering the glans of the penis, is a notable risk factor for the development of penile cancer. Phimosis was observed in 35.2% of penile cancer cases in comparison to 7.6% in the controls. Tobacco use, including smoking, has been determined as an additional risk factor for penile cancer. Smoking has a doseâresponse relationship, where smokers consuming more than 10 cigarettes a day had a significantly higher risk for PC compared to those consuming 1â10 cigarettes a day. HPV prevalence is further enhanced by the number of sexual partners, another prominent PC risk factor.
#17 HPV and Penile Cancer: Epidemiology, Risk Factors, and Clinical Insights
https://www.mdpi.com/2076-0817/13/9/809
Penile cancer (PC) is a rare malignancy predominantly of squamous cell origin. Approximately 40% of penile tumors are associated with human papillomavirus (HPV) infection. Diagnosing PC remains challenging due to its rarity and variety of clinical presentations. Furthermore, the impact of HPV on the tumor immune microenvironment complicates clinical management, although recent advancements in immune checkpoint inhibitors (ICIs) have shown some efficacy in treating HPV-associated PC. Ongoing research efforts aim to develop oncologic treatments that target HPV-induced cellular modifications. Additionally, novel therapeutic vaccines and adoptive T-cell therapies targeting HPV oncoproteins represent emerging treatment modalities. Our review highlights the complex interplay between HPV and penile carcinogenesis, emphasizing its epidemiology, etiology, clinicopathological characteristics, and potential therapeutic implications.
#18 Ten-year surgical experiences with penile cancer at a tertiary care hospital in northwestern Tanzania: a retrospective study of 236 patients | World Journal of Surgical Oncology | Full Text
https://wjso.biomedcentral.com/articles/10.1186/s12957-015-0482-0
Phimosis is considered an important risk factor for the development of penile cancer and is found in approximately 25% to 75% of patients with this cancer in the largest series. […] In our study, more than 60% of patients presented with severe phimosis not allowing the possibility of exposing the glans. […] The majority of patients (89.2%) in this study were uncircumcised. […] HPV has been reported to be a risk factor in the development of penile cancer. […] Several studies have shown an association between penile cancer and smoking. […] The majority of patients in this study presented late with an advanced stage of the disease (Jacksons stages III and IV) with operable or inoperable inguinal metastases and tumors involving adjacent structures or distant metastases which is in keeping with other studies performed in developing countries.
#18 Ten-year surgical experiences with penile cancer at a tertiary care hospital in northwestern Tanzania: a retrospective study of 236 patients | World Journal of Surgical Oncology | Full Text
https://wjso.biomedcentral.com/articles/10.1186/s12957-015-0482-0
The majority of patients (63.1%) underwent partial penectomy. […] HIV positivity, histopathological stage and grade of the tumor, and presence of metastases at the time of diagnosis were the main predictors of death (P0.001). […] Penile cancer is not rare in our environment. […] The majority of patients present late with advanced stage of the disease. […] Early detection of primary cancer at an early stage may improve the prognosis. […] The management of penile cancer in resource-limited countries like Tanzania poses major diagnostic and therapeutic challenges which need to be addressed. […] The outcome of treatment of penile cancer in most developing countries has been poor because the majority of these patients present late to the hospital with advanced stage. […] This study was conducted to describe the pattern and treatment outcome of penile cancer patients treated at our center and to highlight challenges associated with the care of these patients and proffer solutions for improved outcome.
#19 Risks for penile cancer | Canadian Cancer Society
https://cancer.ca/en/cancer-information/cancer-types/penile/risks
Having an infection with human papillomavirus (HPV) is the main risk for penile cancer. […] Penile cancer is not common in Canada. The risk of developing it increases as you get older. It most often happens in men older than 60 years of age, but it can develop at any age. […] The following can increase your risk for penile cancer. There are things you can do to lower your risk and help protect you from developing cancer. […] HPV increases the risk for penile cancer. […] Although there is evidence that circumcision at a young age lowers the risk for penile cancer, there is not enough evidence to recommend it as a way of preventing the disease. […] Phimosis makes it harder to clean the penis well. This can lead to infections or chronic inflammation, which increases your risk for penile cancer. […] Having a weak immune system (immunosuppression) increases your risk for penile cancer. […] Smoking tobacco has been linked with penile cancer, but more research is needed to know for sure that it is a risk. […] Epidemiology and natural history of penile cancer.
#20 Diagnosis, Epidemiology, and Pathology of Penile Cancer | Oncohema Key
https://oncohemakey.com/diagnosis-epidemiology-and-pathology-of-penile-cancer/
The disease is rare before the age of 40 and exceedingly uncommon in adolescents and children. […] Several risk factors have been identified. […] The most important is phimosis, a condition characterized by incapacity to fully retract the foreskin, which is present in more than half of cancer patients. […] A substantially increased risk for penile cancer is observed in phimotic patients. […] Smoking has been related to penile cancer. […] About 40% of penile carcinomas show evidence of human papillomavirus (HPV) DNA, especially high-risk genotypes such as HPV-16, and there is a striking correlation of morphological subtypes of carcinomas showing warty and/or basaloid features and the presence of the virus. […] A third to one half of penile carcinomas are associated with lichen sclerosus, and there is compelling evidence indicating that this condition is specifically associated with some subtypes of cancer (usual, verrucous, papillary, and pseudohyperplastic carcinomas).
#21
https://link.springer.com/article/10.1007/s00345-008-0302-z
Penile cancer is a disease with a high morbidity and mortality. Its prevalence is relatively rare, but the highest in some developing countries. […] Careful monitoring of men with lichen sclerosis, genital Bowens disease, erythroplasia of Queyrat and bowenoid papulosis seems useful, thereby offering early recognition of penile cancer and, subsequently, conservative therapeutic options. […] Further research should not only focus on HPV mediated pathogenic pathways but also on the non-HPV related molecular and genetic factors that play a role in penile cancer development. Options for prevention of penile cancer include (neonatal) circumcision, limitation of penile HPV infections (either by prophylactic vaccination or condom use), prevention of phimosis, treatment of chronic inflammatory conditions, limiting PUVA treatment, smoking cessation and hygienic measures.
#22 Surveillance strategies in the management of penile cancer
https://pmc.ncbi.nlm.nih.gov/articles/PMC5673796/
Penile cancer is a rare disease and can be associated with a high risk of recurrence in regional lymph nodes and distant sites. Surveillance strategies geared towards early detection and treatment are recommended given the significant morbidity and mortality associated with recurrences. […] Given that recurrences may be curable if detected early, close follow up is recommended. […] The risk of recurrence after primary therapy for penile cancer is grade and stage dependent. Therefore, a grade and stage appropriate surveillance strategy is imperative in all patients including those treated with organ-preservation, such as phallus-sparing surgeries (e.g., local excision, glansectomy and distal corporectomy), laser ablation, topical therapies and radiation therapy. […] Thus, continued long term surveillance is recommended in all patients given the high risk of recurrencea predictor of poor overall survival.
#22 Surveillance strategies in the management of penile cancer
https://pmc.ncbi.nlm.nih.gov/articles/PMC5673796/
Regardless of the treatment offered, a more intense surveillance schedule is warranted when compared to low-risk disease, adding periodic cross-sectional imaging as an adjunct to the physical examination. […] Most guidelines, including the European Association of Urology and the National Comprehensive Cancer Network guidelines recommend follow-up visits every 3 months in the first 2 years, every 6 months for years 3 to 5, and annually thereafter. […] Penile cancer is a rare disease, with certain patients having a high risk of recurrence in the inguinal and pelvic lymph nodes. Because of the morbidity and mortality associated with recurrences, a risk-adjusted surveillance strategy geared towards early detection and treatment is recommended.
#23 Surveillance strategies in the management of penile cancer – Salami – Translational Andrology and Urology
https://tau.amegroups.org/article/view/15303/html
Penile cancer is a rare disease and can be associated with a high risk of recurrence in regional lymph nodes and distant sites. Surveillance strategies geared towards early detection and treatment are recommended given the significant morbidity and mortality associated with recurrences. […] Given that recurrences may be curable if detected early, close follow up is recommended. […] The risk of recurrence after primary therapy for penile cancer is grade and stage dependent. Therefore, a grade and stage appropriate surveillance strategy is imperative in all patients including those treated with organ-preservation, such as phallus-sparing surgeries (e.g., local excision, glansectomy and distal corporectomy), laser ablation, topical therapies and radiation therapy. […] Thus, clinical evaluation history and physical examination aimed at early detection of recurrent lesions at the site of the treated primary tumor or elsewhere on the penis should be performed.
#23 Surveillance strategies in the management of penile cancer – Salami – Translational Andrology and Urology
https://tau.amegroups.org/article/view/15303/html
A rigorous follow up schedule, especially in the first 2 years, should be implemented in patients with negative DSNB given the relatively high false negative rates. […] Thus, continued long term surveillance is recommended in all patients given the high risk of recurrence a predictor of poor overall survival. […] Regardless of the treatment offered, a more intense surveillance schedule is warranted when compared to low-risk disease, adding periodic cross-sectional imaging as an adjunct to the physical examination. […] The intensity of follow-up, however, is dependent on the pathological stage and grade of disease and the treatment performed. […] Life-long follow-up is recommended because recurrence can occur beyond 5 years.
#24 EAU Guidelines on Penile Cancer – Uroweb
https://uroweb.org/guidelines/penile-cancer/chapter/followup
Penile cancer has a significant impact on QoL and unfortunately there remain many unmet needs to address (see Table 1.1 in Chapter 1) [2]. […] From an oncological perspective, surveillance is important as early detection of recurrence may increase the likelihood of curative treatment. […] Local or regional nodal recurrences usually occur within two years of primary treatment [147,305,306]. […] Penile cancer has a significant impact on QoL in many ways and there remain many unmet needs to address. […] There is very little data on QoL after treatment for penile cancer. In particular, there is heterogeneity of the psychometric tools used to assess QoL outcomes and further research is needed to develop disease-specific PROMS for penile cancer. […] Access to psychological support, counselling and psychosexual therapy are critical components of a holistic and multi-disciplinary patient support service.
#24 EAU Guidelines on Penile Cancer – Uroweb
https://uroweb.org/guidelines/penile-cancer/chapter/followup
Ideally, following nodal surgery, patients would be referred to specialist lymphoedema services for assessment and management before any significant lymphoedema occurs. […] In one UK specialist penile cancer centre (referral population approximately 11 million), 5-year CSS rates were observed to improve by up to 12-85% following centralisation.
#25 Penile Cancer in: Journal of the National Comprehensive Cancer Network Volume 11 Issue 5 (2013)
https://jnccn.org/view/journals/jnccn/11/5/article-p594.xml?rskey=0RBamL&result=3&print
Squamous cell carcinoma of the penis represents approximately 0.5% of all cancers among men in the United States and other developed countries. […] The incidence is higher (up to 10%) among men in the developing countries of Asia, Africa, and South America. […] Early diagnosis is of utmost importance, because this disease can result in devastating disfigurement and has a 5-year survival rate of approximately 50% (85% for patients with negative lymph nodes and 29%-40% for patients with positive nodes, with the lowest survival rates at 0% for patients with pelvic lymph node (PLN) involvement). […] The presence and extent of regional ILN metastases has been determined to be the single most important prognostic indicator in determining long-term survival in men with invasive penile SCC. […] The involvement of the ILN can be clinically evident (ie, palpable vs nonpalpable), adding to the difficulty in management.
#25 Penile Cancer in: Journal of the National Comprehensive Cancer Network Volume 11 Issue 5 (2013)
https://jnccn.org/view/journals/jnccn/11/5/article-p594.xml?rskey=0RBamL&result=3&print
Patients with pathologic stage T2 or greater were at significant risk (42%-80%) of nodal metastases if they exhibited greater than 50% poorly differentiated cancer and/or vascular invasion, and therefore an inguinal lymph node dissection (ILND) should be recommended. […] Most low-risk patients and intermediate-risk patients without lymphovascular invasion are followed with a surveillance protocol, because the probability of occult micrometastases in ILNs is less than 17%. […] For patients in the high-risk group (T2 or G3) and intermediate-risk patients with lymphovascular invasion, a modified or radical inguinal lymphadenectomy is strongly recommended, because occult metastatic disease ranges between 68% and 73%. […] A large retrospective review of 700 patients found that penile-sparing therapies carry a significantly higher risk of local recurrence (28%) than partial or total penectomy (5%) and thus require closer surveillance. […] Patients without nodal involvement had a regional recurrence rate of 2% compared with 19% for patients with N+ disease.
#26 (PDF) Penile cancer: epidemiology, pathogenesis and prevention
https://www.academia.edu/37944814/Penile_cancer_epidemiology_pathogenesis_and_prevention
Increased awareness among doctors and parents about the importance of non-interference with the physiological foreskin separation process in young boys, and the promotion of safe-sex practices, possibly combined with preadolescent gender-neutral HPV vaccination programs, will likely reduce the frequencies of pathological phimosis and sexually acquired HPV infections and, eventually, reduce the burden of penile cancer at the population level.
#27 Penile Cancer: Case Report
https://clinmedjournals.org/articles/iauc/international-archives-of-urology-and-complications-iauc-4-045.php
Distant metastases are generally uncommon (1-10%) and occur late in the disease. […] Penile SCC can be divided into several subtypes. […] Staging is performed using the TNM penile cancer system developed by the American Joint Committee on Cancer. […] For localized disease, there are sophisticated approaches beyond mere amputation, such as glans-sparing partial penectomy, brachytherapy and reconstructive surgery. […] For metastatic disease in LNs, a curative neoadjuvant multidisciplinary paradigm is feasible instead of a palliative approach. […] Prevention and early detection appear critical. […] In particular, neonatal circumcision, smoking cessation and HPV vaccination may substantially reduce the incidence of PC.
#28 Penile Cancer: Case Report
https://www.clinmedjournals.org/articles/iauc/international-archives-of-urology-and-complications-iauc-4-045.php?jid=iauc
Assessment of lymphatic spread with palpation of inguinal lymph nodes is an essential component of the initial physical exam. Lymphatic spread usually occurs in a predictable course, first to the superficial and deep inguinal nodes, followed by the pelvic, and then periaortic nodes. Distant metastases are generally uncommon (1-10%) and occur late in the disease. […] Staging is performed using the TNM penile cancer system developed by the American Joint Committee on Cancer. Staging is based on depth of tumor invasion, nodal involvement, and distant metastases. […] A logical and effective therapeutic approach to PC is possible despite the lack of randomized trials. For localized disease, there are sophisticated approaches beyond mere amputation, such as glans-sparing partial penectomy, brachytherapy and reconstructive surgery. […] Prevention and early detection appear critical. In particular, neonatal circumcision, smoking cessation and HPV vaccination may substantially reduce the incidence of PC. Indeed, HPV vaccination is already approved in the USA for males aged 9-26 years for preventing genital warts and anal cancer.
#29 Long-term outcomes of penile squamous cell carcinoma in men age â¤50 years old compared with men >50 years old from a single tertiary referral centre: a propensity score matched analysis | International Journal of Impotence Research
https://www.nature.com/articles/s41443-024-00842-5
Overall, PeCa in young adults is an under-investigated field, despite observations of increase in its incidence. […] Public awareness and patient education are important and this could be delivered possibly through schools, social media, mens magazines, billboards, and charity awareness campaigns. […] The DSS, RFS and MFS are similar in the 50y and 50y groups. The overall survival was higher in the younger age group.
#30 HPV and Penile Cancer: Epidemiology, Risk Factors, and Clinical Insights.
https://www.urotoday.review/recent-abstracts/urologic-oncology/penile-cancer/155272-hpv-and-penile-cancer-epidemiology-risk-factors-and-clinical-insights.html
Penile cancer (PC) is a rare malignancy predominantly of squamous cell origin. Approximately 40% of penile tumors are associated with human papillomavirus (HPV) infection. […] Diagnosing PC remains challenging due to its rarity and variety of clinical presentations. […] Furthermore, the impact of HPV on the tumor immune microenvironment complicates clinical management, although recent advancements in immune checkpoint inhibitors (ICIs) have shown some efficacy in treating HPV-associated PC. […] Our review highlights the complex interplay between HPV and penile carcinogenesis, emphasizing its epidemiology, etiology, clinicopathological characteristics, and potential therapeutic implications.
#31 Penile cancer: a local case series and literature review | SMJ
http://www.smj.org.sg/article/penile-cancer-local-case-series-and-literature-review
The delay in diagnosis of penile cancer has been well documented. […] The regional femoral and iliac lymph nodes are the sites of penile carcinoma lymphatic metastasis. […] Accurate staging of the primary lesion is important in making treatment decisions and prognosticates the risk of associated lymph node metastases. […] The presence and extent of inguinal lymph node metastases are the most important prognostic factors for survival in patients with penile SCCs. […] There is increasing evidence that early inguinal lymph node dissection confers a better prognosis compared to surveillance and delayed inguinal dissection. […] In patients with palpable inguinal lymph nodes, fine-needle aspiration cytology (FNAC) is currently recommended at the time of, or immediately after, treatment of the primary tumour.