Zakażenie wirusem brodawczaka ludzkiego (hpv) – Rokowania, prognozy i postęp choroby

Zakażenie wirusem brodawczaka ludzkiego (hpv)
Rokowania, prognozy i postęp choroby

Zakażenie wirusem brodawczaka ludzkiego (HPV) cechuje się zróżnicowanym przebiegiem klinicznym, zależnym od typu wirusa, lokalizacji zakażenia oraz statusu immunologicznego pacjenta. Większość infekcji HPV jest przejściowa, z około 67% eliminacją wirusa w ciągu 12 miesięcy, a mediana czasu do samoistnego oczyszczenia u kobiet z HR-HPV wynosi 14,5 miesiąca. Czynniki takie jak wiek, poziom wiremii oraz status menopauzalny wpływają na tempo eliminacji wirusa. Przetrwałe zakażenie HPV wysokiego ryzyka wiąże się ze zwiększonym ryzykiem rozwoju zmian przednowotworowych (CIN2/CIN3) oraz raka szyjki macicy, z 4% skumulowanym ryzykiem rozwoju raka w ciągu 6 lat u kobiet HPV-dodatnich. Status HPV, w tym obecność i integracja DNA HPV16/18, stanowi niezależny czynnik prognostyczny w raku szyjki macicy, gdzie negatywny status HPV lub integracja DNA HPV16/18 korelują z gorszym rokowaniem (OR do 8,9 w 5-letniej obserwacji). W diagnostyce i monitorowaniu zaleca się coroczne badania przesiewowe u kobiet z pozytywnym wynikiem testu na HPV wysokiego ryzyka, natomiast u kobiet HPV-ujemnych odstępy można wydłużyć do co najmniej 5 lat.

Prognoza zakażenia wirusem brodawczaka ludzkiego (HPV)

Spontaniczne ustępowanie infekcji HPV
Czynniki wpływające na prognozę zakażenia HPV
HPV a nowotwory – prognozy długookresowe
Prognozy dla nowotworów związanych z HPV
Prognozy dla pacjentów z niedoborami odporności
Implikacje dla praktyki klinicznej
Podsumowanie prognozy zakażenia HPV
Kolejne rozdziały

Prognoza zakażenia wirusem brodawczaka ludzkiego (HPV)

Zakażenie wirusem brodawczaka ludzkiego (HPV) jest bardzo powszechne, a jego naturalny przebieg i prognozy różnią się znacząco w zależności od typu wirusa, lokalizacji zakażenia oraz statusu immunologicznego pacjenta. Prognozy dla pacjentów zakażonych HPV mogą się znacznie różnić, od spontanicznego ustąpienia infekcji do rozwinięcia się stanu przedrakowego lub nowotworowego.¹²

Spontaniczne ustępowanie infekcji HPV

Większość zakażeń HPV ma charakter przejściowy i ustępuje samoistnie dzięki odpowiedzi immunologicznej organizmu. Badania pokazują, że około 67% infekcji ustępuje w ciągu 12 miesięcy, choć tempo eliminacji wirusa może się różnić w zależności od wieku pacjenta i typu HPV.¹ W przypadku brodawek narządów płciowych dane wskazują, że mogą one samoistnie ustępować, pozostawać niezmienione lub zwiększać swoją wielkość. Około dwie trzecie pacjentów z brodawkami nienaczyniowymi skórnymi doświadcza spontanicznej regresji w ciągu 2 lat, choć mogą pojawić się nowe zmiany.²

W badaniu nad zakażeniem wysokiego ryzyka HPV (HR-HPV) u kobiet bez zmian w szyjce macicy wykazano, że wskaźnik samoistnego oczyszczenia organizmu z wirusa wynosił 51,5%, a mediana czasu do eliminacji wirusa wynosiła 14,5 miesiąca.³ Czynniki znacząco wpływające na tempo eliminacji HPV to między innymi menopauza i przebyte ciąże.⁴

Czynniki wpływające na prognozę zakażenia HPV

Identyfikacja czynników ryzyka przetrwania zakażenia HPV jest kluczowa dla określenia prognozy. Badania wykazały, że wiek i początkowy poziom wiremii są niezależnymi czynnikami ryzyka dla samoistnego ustąpienia zakażenia HPV, ze współczynnikami regresji odpowiednio 0,071 i 0,002.⁵ Oznacza to, że kobiety w starszym wieku lub te z wysokim początkowym poziomem wiremii mają wyższy wskaźnik przetrwałego zakażenia HR-HPV.⁶

Początkowy poziom wiremii może być klinicznie rozważany jako czynnik przesiewowy u kobiet z wysokim ryzykiem rozwoju CIN (śródnabłonkowej neoplazji szyjki macicy) oraz jako wskaźnik kontrolny dla kobiet z zakażeniem HPV wysokiego ryzyka i prawidłową cytologią.⁷ Wykazano również, że poziom wiremii HPV-16 ma znaczenie kliniczne w przewidywaniu zmian szyjki macicy wysokiego stopnia (CIN2/CIN3), a poziom wiremii HPV różni się znacząco w zmianach niskiego stopnia (LSIL) i wysokiego stopnia (HSIL).⁸

HPV a nowotwory – prognozy długookresowe

Długoterminowe badania wskazują, że kobiety z przetrwałym zakażeniem HPV wysokiego ryzyka mają zwiększone ryzyko rozwoju raka szyjki macicy. Badania pokazały, że kobiety z zakażeniem HPV wysokiego ryzyka miały 4% skumulowane ryzyko rozwoju raka szyjki macicy w ciągu 6 lat, podczas gdy kobiety z wynikiem negatywnym miały znikome ryzyko.⁹¹⁰

Skumulowana zapadalność na zmiany wysokiego stopnia (HSIL) lub nowotwór in situ/inwazyjny u kobiet z wynikiem HPV-dodatnim wynosiła odpowiednio 5,6% i 3,7%, natomiast u kobiet z wynikiem HPV-ujemnym wynosiła odpowiednio 0,3% i 0%.¹¹ Inne badania pokazują, że 4-, 5- i 6-letnia skumulowana zapadalność na HSIL lub powyżej wynosiła odpowiednio 3,9%, 4,9% i 10% u kobiet HPV-dodatnich, w porównaniu do 0,09%, 0,26% i 0,34% u kobiet HPV-ujemnych.¹²

Prognozy dla nowotworów związanych z HPV

Rak szyjki macicy

Status HPV jest silnym wyznacznikiem prognozy raka szyjki macicy w okresie do 15 lat po diagnozie.¹³ Badacze sugerują, że testowanie guzów szyjki macicy na obecność HPV powinno być rozważone w rutynowej diagnostyce klinicznej raka szyjki macicy, aby poprawić informacje prognostyczne dla klinicystów i pacjentek.¹⁴

W nowotworach szyjki macicy wykazano, że status HPV DNA, stan fizyczny DNA HPV 16/18 (episomalny/zintegrowany), stadium choroby i wiek są niezależnymi czynnikami prognostycznymi. Pacjentki z negatywnym statusem HPV lub obecnością integracji DNA HPV 16/18 miały gorsze rokowanie – iloraz szans (OR) niekorzystnego wyniku był kilkakrotnie wyższy i osiągał 8,9 (95% CI, 2,9–27,6; p = 0,0001) w okresie 5 lat.¹⁵ Analiza wieloczynnikowa potwierdziła te obserwacje, identyfikując trzy niezależne predyktory wyniku klinicznego miejscowo zaawansowanego raka szyjki macicy: obecność/brak biomarkera (status HPV-ujemny lub integracja DNA HPV16/18) (p = 1,2 × 10−4; OR = 9,67), stadium choroby (p = 0,001; OR = 4,69) oraz wiek (p = 0,025; OR = 0,61).¹⁶

Opracowane modele radiomiczne oparte na uczeniu maszynowym, wykorzystujące obrazy MRI przed leczeniem, mogą wykrywać status karcinogennego HPV z dokładnością dyskryminacyjną, co może mieć znaczenie prognostyczne.¹⁷ Chociaż rola prognostyczna HPV w raku szyjki macicy została potwierdzona w kompleksowej metaanalizie, niektóre badania wskazują, że status HPV nie ma znaczenia prognostycznego.¹⁸

Rak gardła środkowego

W przypadku raka gardła środkowego (OPC) zakażenie HPV jest silnym czynnikiem prognostycznym. Nowotwory HPV-dodatnie wiążą się z lepszą odpowiedzią na terapię i lepszym rokowaniem w porównaniu do nowotworów wywołanych przez tytoń/alkohol.¹⁹ Pacjenci z HPV-dodatnim rakiem gardła środkowego wykazują znacząco dłuższy czas przeżycia (p = 0,0008) oraz statystycznie istotną różnicę w prawdopodobieństwie przeżycia wolnego od choroby i całkowitego przeżycia w porównaniu do pacjentów HPV-ujemnych (odpowiednio p = 0,0045 i p = 0,0037).²⁰

Co ważne, poziom limfocytów naciekających guz (TIL) może dodatkowo stratyfikować pacjentów HPV-dodatnich na grupy wysokiego i niskiego ryzyka. 3-letnie przeżycie dla guzów HPV-dodatnich/TIL-wysokich wynosiło 96% w porównaniu do 76% dla HPV-dodatnich/TIL-umiarkowanych i 59% dla HPV-dodatnich/TIL-niskich. Guzy HPV-dodatnie/TIL-niskie miały podobne przeżycie do guzów HPV-ujemnych (3-letnie przeżycie 56%).²¹ Badania sugerują, że odpowiedź immunologiczna, odzwierciedlona przez poziomy TIL w guzie pierwotnym, odgrywa istotną rolę w poprawie przeżycia obserwowanej u większości pacjentów HPV-dodatnich.²²

Model prognostyczny oparty na niskich poziomach TIL, intensywnym paleniu i późnym stadium T jest niezwykle skuteczny w identyfikowaniu grupy pacjentów HPV-dodatnich z niskim wskaźnikiem przeżycia.²³

Prognozy dla pacjentów z niedoborami odporności

Pacjenci z niedoborami odporności, w tym osoby zakażone HIV lub po przeszczepach narządów, mają gorsze rokowanie w kontekście zakażenia HPV. Badania wykazały konsekwentny związek między zakażeniem HIV a zakażeniem HPV i przedrakowymi zmianami szyjki macicy, a w metaanalizie sześciu badań populacyjnych zgłoszono znacznie wyższy wskaźnik raka szyjki macicy u kobiet z HIV/AIDS (współczynnik zapadalności: 5,8).²⁴

Terapia antyretrowirusowa (ART) i wysoce aktywna terapia antyretrowirusowa (HAART) nie wydają się zmniejszać częstości występowania raka szyjki macicy u kobiet z HIV/AIDS, a przegląd systematyczny wykazał, że ryzyko inwazyjnego raka szyjki macicy zwiększyło się od czasu wprowadzenia HAART.²⁵

U biorców przeszczepów narządów większość badań populacyjnych wykazała wyższą częstość występowania raka szyjki macicy niż u osób z prawidłową odpornością.²⁶ Istnieją również dowody na wyższą zapadalność na śródnabłonkową neoplazję szyjki macicy (CIN) u biorców przeszczepów narządów.²⁷

Przewiduje się, że obciążenie nowotworami związanymi z HPV wzrośnie u kobiet HIV-dodatnich, biorąc pod uwagę skuteczne przedłużenie życia dzięki ART i potencjalnie dłuższy czas trwania przetrwałego zakażenia HPV.²⁸

Implikacje dla praktyki klinicznej

Status HPV i charakterystyka zakażenia HPV mają istotne implikacje dla praktyki klinicznej, szczególnie w zakresie strategii badań przesiewowych i monitorowania pacjentów.

W przypadku kobiet HPV-ujemnych, ryzyko rozwoju raka szyjki macicy jest minimalne. Badania wykazały, że kobiety z negatywnym wynikiem testu na HPV mogą bezpiecznie wydłużyć odstęp między badaniami przesiewowymi do co najmniej 5 lat.²⁹³⁰ Natomiast kobiety z pozytywnym wynikiem testu na HPV wysokiego ryzyka powinny być poddawane corocznym badaniom przesiewowym.³¹

W przypadku pacjentów z nowotworami głowy i szyi związanymi z HPV, status HPV może pomóc w stratyfikacji ryzyka i dostosowaniu schematu leczenia. Bezpośrednie wykrycie DNA HPV przy użyciu PCR lub ISH może być wiarygodnie stosowane jako zastępcze biomarkery HPV u pacjentów z rakiem gardła środkowego, z istotną wartością prognostyczną.³²

Status HPV przed leczeniem i zmiany w statusie HPV po leczeniu mają wpływ na rokowanie. Utrzymująca się pozytywność HPV u pacjentów po radioterapii jest złym czynnikiem prognostycznym.³³

Podsumowanie prognozy zakażenia HPV

Typ zakażenia/kontekst kliniczny	Prognoza	Czynniki modyfikujące
Zakażenie HPV bez zmian cytologicznych	51,5% spontanicznego ustąpienia, mediana czasu do eliminacji: 14,5 miesiąca	Wiek, początkowy poziom wiremii, status menopauzalny
Brodawki narządów płciowych	Ok. 2/3 ustępuje samoistnie w ciągu 2 lat	Status immunologiczny, typ HPV
HPV wysokiego ryzyka (nie 16/18) z LSIL	Niskie ryzyko CIN3+ w porównaniu z punktem odniesienia 12-miesięcznej obserwacji	Wiek, status cytologiczny
HPV wysokiego ryzyka – ryzyko kumulacyjne	4% skumulowane ryzyko raka szyjki macicy w ciągu 6 lat	Typ HPV, status cytologiczny, wiek
Rak gardła środkowego HPV-dodatni	Lepsza odpowiedź na terapię i lepsze rokowanie (3-letnie przeżycie 59-96%)	Poziom TIL, palenie tytoniu, stadium T
Rak szyjki macicy HPV-dodatni vs. HPV-ujemny	Lepsze rokowanie dla HPV-dodatnich (zintegrowane DNA HPV16/18 lub negatywność HPV – gorsze rokowanie)	Status integracji DNA HPV, stadium choroby, wiek
Zakażenie HPV u osób z niedoborem odporności (HIV/AIDS, po przeszczepie)	Wyższe ryzyko przetrwałego zakażenia i progresji do nowotworu	Status immunologiczny, terapia antyretrowirusowa

Podsumowując, zakażenie HPV jest złożonym procesem, a jego prognoza zależy od wielu czynników, w tym typu wirusa, statusu immunologicznego pacjenta, lokalizacji zakażenia oraz obecności dodatkowych czynników ryzyka. W większości przypadków zakażenie HPV ustępuje samoistnie, jednak przetrwałe zakażenie typami wysokiego ryzyka może prowadzić do rozwoju nowotworów. Status HPV jest istotnym czynnikiem prognostycznym w przypadku nowotworów związanych z HPV, z generalnie lepszym rokowaniem dla pacjentów HPV-dodatnich, szczególnie w przypadku raka gardła środkowego. Wyjątkiem jest rak szyjki macicy z zintegrowanym DNA HPV16/18, który wiąże się z gorszym rokowaniem.³⁴³⁵

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 Human Papillomavirus (HPV): Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/219110-overview
HPV infection primarily involves the basal epithelial cells, leading to common recurrences and regressions. The prognosis generally is good, and most cases of genital warts are treatable. However, patients who do not develop immunity to HPV may face potentially serious sequelae. […] Genital warts can spontaneously regress, remain unchanged, or increase in size. Treating these lesions does not impact the development of cervical cancer. Approximately two-thirds of patients with nongenital cutaneous warts experience spontaneous regression within 2 years, although new warts may appear. […] HPV infection of the vulva can result in vulvar intraepithelial neoplasia (dysplasia) or squamous cell carcinoma of the vulva. Most research indicates a strong association between HPV infection and the development of cervical dysplasia and cervical carcinoma. HPV accounts for more than 99% of the attributable risk for cervical dysplasia.
#1 Oncogenic HPV types not 16/18 | Cancer Council
https://www.cancer.org.au/clinical-guidelines/cervical-cancer/cervical-cancer-screening/management-of-oncogenic-hpv-test-results/oncogenic-hpv-types-not-16-18
Women who have a positive oncogenic human papillomavirus (HPV) test result for which HPV types other than 16 and/or 18 are detected (HPV not 16/18), should be managed according to the recommendations in this section. […] HPV infections typically clear rapidly. Overall, an estimated 67% of infections resolve by 12 months, although the rate of resolution probably varies between age groups and by HPV type. After viral clearance (i.e. oncogenic HPV is no longer detected), women are at very low risk of significant cervical disease for the next 5 years. Therefore, if women with a positive oncogenic HPV (not 16/18) test result are not referred to colposcopy immediately, 12 months is an appropriate follow-up interval for retesting and allows for viral clearance to occur in a proportion of women.
#2 Risk factors for human papillomavirus infection, cervical intraepithelial neoplasia and cervical cancer: an umbrella review and follow-up Mendelian randomisation studies | BMC Medicine | Full Text
https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-023-02965-w
Persistent infection by oncogenic human papillomavirus (HPV) is necessary although not sufficient for development of cervical cancer. […] Our main analysis supported the association of systemic (HIV infection, immunosuppressive medications) and local immunosuppression (altered vaginal microbiota) with increased risk for worse HPV and cervical disease outcomes. […] We identified meta-analyses with strong, highly suggestive, and suggestive evidence for an increased risk of hrHPV and cervical cancer incidence in HIV-positive women, when compared to the general population. […] There is consistently strong and highly suggestive evidence that HIV positivity reduces HPV clearance rates and increases the risk of HPV infection and cervical cancer development.
#2 Human Papillomavirus (HPV): Practice Essentials, Background, Pathophysiology
https://emedicine.medscape.com/article/219110-overview
HPV infection primarily involves the basal epithelial cells, leading to common recurrences and regressions. The prognosis generally is good, and most cases of genital warts are treatable. However, patients who do not develop immunity to HPV may face potentially serious sequelae. […] Genital warts can spontaneously regress, remain unchanged, or increase in size. Treating these lesions does not impact the development of cervical cancer. Approximately two-thirds of patients with nongenital cutaneous warts experience spontaneous regression within 2 years, although new warts may appear. […] HPV infection of the vulva can result in vulvar intraepithelial neoplasia (dysplasia) or squamous cell carcinoma of the vulva. Most research indicates a strong association between HPV infection and the development of cervical dysplasia and cervical carcinoma. HPV accounts for more than 99% of the attributable risk for cervical dysplasia.
#3 Outcome and associated factors of high-risk human papillomavirus infection without cervical lesions | BMC Women’s Health | Full Text
https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-023-02764-8
To study the outcome of human papillomavirus (HPV) infection in women with cervical pathology results of non-cervical intraepithelial neoplasia (CIN) or cervical cancer and positive high-risk HPV test, as well as analyze the associated risk factors affecting the outcome of infection. […] The spontaneous clearance rate of HR-HPV infection was 51.5%, and the median time to viral clearance was 14.5 months. […] Age and the initial viral load were high risk factors affecting the spontaneous clearance of HR-HPV infection. […] In women with normal or low-grade lesions on the cell smear, the spontaneous clearance rate of HR-HPV infection was 51.5% and the time to clearance was 14.5 months. […] These findings suggest that non-young women or those with high viral loads have a higher rate of persistent HR-HPV infection.
#4 Outcome and associated factors of high-risk human papillomavirus infection without cervical lesions | BMC Women’s Health | Full Text
https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-023-02764-8
The factors significantly associated with HPV clearance rate and time to HPV clearance consisted of menopause and full-term delivery. […] Age and initial viral load were found to be independent risk factors for the spontaneous clearance of HPV with regression coefficients of 0.071 and 0.002, respectively. […] The initial viral load may be clinically considered for screening women with high-risk factors for the development of CIN and as a follow-up indicator for women with high-risk HPV infection and normal cytology. […] Therefore, an aggressive screening approach is an appropriate recommendation.
#5 Outcome and associated factors of high-risk human papillomavirus infection without cervical lesions | BMC Women’s Health | Full Text
https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-023-02764-8
The factors significantly associated with HPV clearance rate and time to HPV clearance consisted of menopause and full-term delivery. […] Age and initial viral load were found to be independent risk factors for the spontaneous clearance of HPV with regression coefficients of 0.071 and 0.002, respectively. […] The initial viral load may be clinically considered for screening women with high-risk factors for the development of CIN and as a follow-up indicator for women with high-risk HPV infection and normal cytology. […] Therefore, an aggressive screening approach is an appropriate recommendation.
#6 Outcome and associated factors of high-risk human papillomavirus infection without cervical lesions | BMC Women’s Health | Full Text
https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-023-02764-8
To study the outcome of human papillomavirus (HPV) infection in women with cervical pathology results of non-cervical intraepithelial neoplasia (CIN) or cervical cancer and positive high-risk HPV test, as well as analyze the associated risk factors affecting the outcome of infection. […] The spontaneous clearance rate of HR-HPV infection was 51.5%, and the median time to viral clearance was 14.5 months. […] Age and the initial viral load were high risk factors affecting the spontaneous clearance of HR-HPV infection. […] In women with normal or low-grade lesions on the cell smear, the spontaneous clearance rate of HR-HPV infection was 51.5% and the time to clearance was 14.5 months. […] These findings suggest that non-young women or those with high viral loads have a higher rate of persistent HR-HPV infection.
#7 Outcome and associated factors of high-risk human papillomavirus infection without cervical lesions | BMC Women’s Health | Full Text
https://bmcwomenshealth.biomedcentral.com/articles/10.1186/s12905-023-02764-8
The factors significantly associated with HPV clearance rate and time to HPV clearance consisted of menopause and full-term delivery. […] Age and initial viral load were found to be independent risk factors for the spontaneous clearance of HPV with regression coefficients of 0.071 and 0.002, respectively. […] The initial viral load may be clinically considered for screening women with high-risk factors for the development of CIN and as a follow-up indicator for women with high-risk HPV infection and normal cytology. […] Therefore, an aggressive screening approach is an appropriate recommendation.
#8 HPV Viral Load in Predicting the Prognosis of LSIL | Clinical Research Trial Listing
https://www.centerwatch.com/clinical-trials/listings/NCT05051852/hpv-viral-load-in-predicting-the-prognosis-of-lsil?q=lsil
Human papillomavirus (HPV) infection has become one of the most important health problems faced by women all over the world. […] Among them, the persistent infection of high-risk human papillomavirus (HR-HPV) is closely related to the occurrence of invasive cervical cancer. […] In addition, other studies have shown that HPV-16 viral load has certain clinical significance in predicting Cin2 / CIN3 high-grade cervical lesions, and HPV viral load level is significantly different in cervical low-grade squamous intraepithelial lesion (LSIL) and cervical high-grade squamous intraepithelial lesion (HSIL). […] It can be seen that the study of the relationship between HPV viral load and cervical lesions is of great significance for clinical disease development prediction and cervical cancer screening.
#9 Long-term outcomes of high-risk human papillomavirus infection support a long interval of cervical cancer screening
https://pmc.ncbi.nlm.nih.gov/articles/PMC2266853/
Knowing that infection of high-risk human papillomavirus (HPV) causes virtually all cervical cancer (CC), the long-term outcomes of HPV infection, especially the absolute risk and time lapse of developing CC, are beyond the scope of ordinary follow-up study owing to ethical concerns. […] The cumulative incidences of high-grade squamous intraepithelial lesion (HSIL) and in situ/invasive cancer in HPV-positive women were 5.6 and 3.7%, respectively, and those in HPV-negative women were 0.3 and 0%. […] The study showed that women with a prevalent infection of high-risk HPV had a 4% cumulative risk for CC in 6 years, whereas those tested negative had little risk. […] The results thus figure the real natural history of HPV infection in the population in Taiwan. […] In contrast to the occurrence of HSIL and cancer, which was highly associated with HPV infection at enrolment, in this study and that of the Manchester cohort, the occurrence of LSIL was found to be unrelated to the initial HPV status.
#10 Long-term outcomes of high-risk human papillomavirus infection support a long interval of cervical cancer screening | British Journal of Cancer
https://www.nature.com/articles/6604262
Knowing that infection of high-risk human papillomavirus (HPV) causes virtually all cervical cancer (CC), the long-term outcomes of HPV infection, especially the absolute risk and time lapse of developing CC, are beyond the scope of ordinary follow-up study owing to ethical concerns. […] The study showed that women with a prevalent infection of high-risk HPV had a 4% cumulative risk for CC in 6 years, whereas those tested negative had little risk. […] A major but rarely studied outcome measure is the absolute risk and sojourn time of developing cervical cancer (CC) or its precursor in the presence of HPV infection. […] The 4-, 5- and 6-year cumulative incidences of HSIL or above neoplasia were 3.9, 4.9 and 10%, respectively, in HPV-positive women, as compared to 0.09, 0.26 and 0.34% in the HPV-negative women.
#11 Long-term outcomes of high-risk human papillomavirus infection support a long interval of cervical cancer screening
https://pmc.ncbi.nlm.nih.gov/articles/PMC2266853/
Knowing that infection of high-risk human papillomavirus (HPV) causes virtually all cervical cancer (CC), the long-term outcomes of HPV infection, especially the absolute risk and time lapse of developing CC, are beyond the scope of ordinary follow-up study owing to ethical concerns. […] The cumulative incidences of high-grade squamous intraepithelial lesion (HSIL) and in situ/invasive cancer in HPV-positive women were 5.6 and 3.7%, respectively, and those in HPV-negative women were 0.3 and 0%. […] The study showed that women with a prevalent infection of high-risk HPV had a 4% cumulative risk for CC in 6 years, whereas those tested negative had little risk. […] The results thus figure the real natural history of HPV infection in the population in Taiwan. […] In contrast to the occurrence of HSIL and cancer, which was highly associated with HPV infection at enrolment, in this study and that of the Manchester cohort, the occurrence of LSIL was found to be unrelated to the initial HPV status.
#12 Long-term outcomes of high-risk human papillomavirus infection support a long interval of cervical cancer screening | British Journal of Cancer
https://www.nature.com/articles/6604262
Knowing that infection of high-risk human papillomavirus (HPV) causes virtually all cervical cancer (CC), the long-term outcomes of HPV infection, especially the absolute risk and time lapse of developing CC, are beyond the scope of ordinary follow-up study owing to ethical concerns. […] The study showed that women with a prevalent infection of high-risk HPV had a 4% cumulative risk for CC in 6 years, whereas those tested negative had little risk. […] A major but rarely studied outcome measure is the absolute risk and sojourn time of developing cervical cancer (CC) or its precursor in the presence of HPV infection. […] The 4-, 5- and 6-year cumulative incidences of HSIL or above neoplasia were 3.9, 4.9 and 10%, respectively, in HPV-positive women, as compared to 0.09, 0.26 and 0.34% in the HPV-negative women.
#13 HPV Infection Determines Prognosis in Patients with Invasive Cervical Cancer
https://www.targetedonc.com/view/hpv-infection-determines-prognosis-in-patients-with-invasive-cervical-cancer
High risk human papillomavirus infection appears to be a strong determinant of cervical cancer prognosis over 15 years after diagnosis. […] High risk human papillomavirus infection reveals (hrHPV) to be a strong determinant of cervical cancer prognosis over 15 years after diagnosis. […] Investigators determined that tumor hrHPV status is a novel biomarker with strong prognostic value for patients with ICC. To improve prognostic information for clinicians and women, investigators suggest HPV testing of cervical tumors should be considered in the routine clinical workup of cervical cancer.
#14 HPV Infection Determines Prognosis in Patients with Invasive Cervical Cancer
https://www.targetedonc.com/view/hpv-infection-determines-prognosis-in-patients-with-invasive-cervical-cancer
High risk human papillomavirus infection appears to be a strong determinant of cervical cancer prognosis over 15 years after diagnosis. […] High risk human papillomavirus infection reveals (hrHPV) to be a strong determinant of cervical cancer prognosis over 15 years after diagnosis. […] Investigators determined that tumor hrHPV status is a novel biomarker with strong prognostic value for patients with ICC. To improve prognostic information for clinicians and women, investigators suggest HPV testing of cervical tumors should be considered in the routine clinical workup of cervical cancer.
#15 HPV Status and Individual Characteristics of Human Papillomavirus Infection as Predictors for Clinical Outcome of Locally Advanced Cervical Cancer
https://www.mdpi.com/2075-4426/11/6/479
HPV status was determined in scrapings from the cervix of 173 CC patients before treatment. The tumors of 20 patients (11.5%) were HPV-negative for 14 high risk genotypes. HPV types 16 or 18 were detected in 115 patients (66.5%). A small proportion of HPV-negative tumors were found in almost all studies using highly sensitive HPV tests. Until now, the question of the existence of true HPV negative CC remains controversial. […] The presence of HPV 16/18 DNA integration of various degrees into the cell genome (integrated form) was found in the majority of patientsâin 66 cases (57.4%), of which 26 cases had complete (100%) integration of viral DNA. Absence of integration (episomal form) was registered in 49 (42.6%) patients. […] The study results served as the basis for combining patients with integrated HPV16/18 DNA (regardless of the degree of integration) and HPV-negative patients into one prognostic group. As a result of this combining, a single biomarker including HPV-negativity or presence of HPV16/18 DNA integration into the cell genome was created. In the general group of CC patients with stages IIâIII, OR of unfavorable outcome was several times higher in patients with presence of the biomarker than in other patients, and reached 8.9 (95% CI, 2.9â27.6; p = 0.0001) for period of 5 years.
#16 HPV Status and Individual Characteristics of Human Papillomavirus Infection as Predictors for Clinical Outcome of Locally Advanced Cervical Cancer
https://www.mdpi.com/2075-4426/11/6/479
Multivariate analysis included all variables regardless of statistical significance on univariate analysis: clinical and morphological characteristics (age, FIGO stage, histological type, nuclear grade, form of tumor growth, parametrial infiltration, metastases in lymph nodes, treatment method) and molecular genetic parameters of HPV infection (presence/absence of the biomarker, HPV genotype, number of genotypes, VL). As a result of multivariate analysis, three independent predictors of clinical outcome of locally advanced CC were identified: presence/absence of the biomarker (HPV-negative status or HPV16/18 DNA integration) (p = 1.2 Ã 10â4; OR = 9.67), stage of the disease (p = 0.001; OR = 4.69), age (p = 0.025; OR = 0.61). […] Thus, based on the results obtained, it is possible with high accuracy to predict clinical outcome (progression) of locally advanced cervical cancer according to the following criteria: HPV DNA status (negative/positive), physical state of HPV 16/18 DNA (episomal/integrated), stage of the disease, age. The application of our model in clinical practice makes it possible to identify CC patients with a high risk of disease progression in order to personalize treatment approaches in the future.
#17 Prediction of carcinogenic human papillomavirus types in cervical cancer from multiparametric magnetic resonance images with machine learning-based radiomics models – Diagnostic and Interventional Radiology
https://www.dirjournal.org/articles/prediction-of-carcinogenic-human-papillomavirus-types-in-cervical-cancer-from-multiparametric-magnetic-resonance-images-with-machine-learning-based-radiomics-models/doi/dir.2022.221335
Machine learning-based radiomics models based on pre-treatment MRI can detect carcinogenic HPV status with discriminative accuracy. […] Prediction of carcinogenic human papillomavirus (HPV) oncogenes enables the identification of high-risk patients and can be used as a prognostic marker. […] Machine learning-based radiomics models can predict carcinogenic HPV DNA status in cervical cancer. […] Several studies in the literature report that HPV DNA status is associated with treatment response, disease-free survival, and overall survival in patients with cervical carcinoma. […] A recently published meta-analysis indicated that positive HPV DNA status favors good prognosis in cervical cancer. […] Although the prognostic role of HPV in cervical cancer has been reported in a comprehensive meta-analysis, several studies have shown that HPV status does not have any prognostic significance.
#18 Prediction of carcinogenic human papillomavirus types in cervical cancer from multiparametric magnetic resonance images with machine learning-based radiomics models – Diagnostic and Interventional Radiology
https://www.dirjournal.org/articles/prediction-of-carcinogenic-human-papillomavirus-types-in-cervical-cancer-from-multiparametric-magnetic-resonance-images-with-machine-learning-based-radiomics-models/doi/dir.2022.221335
Machine learning-based radiomics models based on pre-treatment MRI can detect carcinogenic HPV status with discriminative accuracy. […] Prediction of carcinogenic human papillomavirus (HPV) oncogenes enables the identification of high-risk patients and can be used as a prognostic marker. […] Machine learning-based radiomics models can predict carcinogenic HPV DNA status in cervical cancer. […] Several studies in the literature report that HPV DNA status is associated with treatment response, disease-free survival, and overall survival in patients with cervical carcinoma. […] A recently published meta-analysis indicated that positive HPV DNA status favors good prognosis in cervical cancer. […] Although the prognostic role of HPV in cervical cancer has been reported in a comprehensive meta-analysis, several studies have shown that HPV status does not have any prognostic significance.
#19 HPV Status as Prognostic Biomarker in Head and Neck CancerâWhich Method Fits the Best for Outcome Prediction?
https://www.mdpi.com/2072-6694/13/18/4730
HPV infection is associated with better therapeutic response and outcome compared to tobacco/alcohol-induced cancers. […] P16-IHC alone showed the best performance for discriminating between good (high expression) vs poor outcome (low expression; p = 0.0030) in OPSCC patients. […] HPV-DNA-ISH (p = 0.0039), HPV-DNA-PCR (p = 0.0113), and p16-Ki67 dual stain (p = 0.0047) were significantly associated with prognosis in uni- and multivariable analysis for oropharyngeal cancer. […] P16 positivity (i.e., IRS â¥ 7; OR = 2.897; 95% CI 1.254â7.172), HPV-DNA-PCR positivity (OR = 2.383; 95% CI 1.100â6.162), HPV-DNA-ISH positivity (OR = 6.126; 95% CI 1.536â41.22), and p16-Ki67-dual-stain positivity (OR = 3.423; 95% CI 1.358â9.565) each independently predicted survival probability. […] HPV-related head and neck cancers are associated with better response to radiotherapy and chemoradiotherapy, as well as improved overall survival, compared to tobacco-/alcohol-associated disease.
#20 Human papillomavirus infection predicts a better survival rate in patients with oropharyngeal cancer
https://pmc.ncbi.nlm.nih.gov/articles/PMC8425231/
Squamous cell carcinoma is the most common malignant tumour occurring in the head and neck region. It is now understood that (human papillomavirus (HPV)- positive and HPV-negative diseases are two very different clinical entities associated with different outcomes. […] The observation time for HPV-positive patients was significantly longer (p = 0.0008). […] A statistically significant difference in the disease-free survival probability and overall survival probability between HPV-positive and HPV-negative patients was found (p = 0.0045 and p = 0.0037 respectively). […] Our data show that HPV infection is a predictor of better disease-free and overall survival in patients with oropharyngeal cancer. […] The total observation time is longer than 10 years for HPV-positive OPC patients.
#21 Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer | British Journal of Cancer
https://www.nature.com/articles/bjc2013639
In unstratified OPSCC, high TIL levels predicted for survival and correlated significantly with HPV-positive tumours. […] The 3-year survival for HPV-positive/TILhigh tumours was 96% compared with 76% for HPV-positive/TILmod and 59% for HPV-positive/TILlow. The HPV-positive/TILlow tumours had similar survival to HPV-negative tumours (3-year survival, 56%). […] A prognostic model based on low TIL levels, heavy smoking, and late T stage is extremely effective at identifying a group of HPV-positive patients with poor survival.
#22 Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer | British Journal of Cancer
https://www.nature.com/articles/bjc2013639
Human papillomavirus (HPV)-positive oropharyngeal cancer (OPSCC) is associated with improved survival compared with HPV-negative disease. However, a minority of HPV-positive patients have poor prognosis. Currently, there is no generally accepted strategy for identifying these patients. […] Patients with HPV-positive tumours showed improved survival (hazard ratio (HR), 0.33 (0.210.53)). High levels of tumour-infiltrating lymphocytes (TILs) stratified HPV-positive patients into high-risk and low-risk groups (3-year survival; HPV-positive/TILhigh=96%, HPV-positive/TILlow=59%). […] Our data suggest that an immune response, reflected by TIL levels in the primary tumour, has an important role in the improved survival seen in most HPV-positive patients, and is relevant for the clinical evaluation of HPV-positive OPSCC.
#23 Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer | British Journal of Cancer
https://www.nature.com/articles/bjc2013639
In unstratified OPSCC, high TIL levels predicted for survival and correlated significantly with HPV-positive tumours. […] The 3-year survival for HPV-positive/TILhigh tumours was 96% compared with 76% for HPV-positive/TILmod and 59% for HPV-positive/TILlow. The HPV-positive/TILlow tumours had similar survival to HPV-negative tumours (3-year survival, 56%). […] A prognostic model based on low TIL levels, heavy smoking, and late T stage is extremely effective at identifying a group of HPV-positive patients with poor survival.
#24 16. Screening in immune-deficient women | Cancer Council
https://www.cancer.org.au/clinical-guidelines/cervical-cancer/cervical-cancer-screening/screening-in-immune-deficient-women
Cervical prevalence of oncogenic human papillomavirus (HPV) in HIV-positive women without cytological abnormalities is higher than their counterparts from the general population. […] HIV infection has been consistently associated with HPV infection and pre-cancerous cervical lesions, and a significantly higher rate of cervical cancer in women with HIV/acquired immune deficiency syndrome (AIDS) was reported in a meta-analysis of six population-based studies (incidence ratio: 5.8). […] High incidence rates of cervical cancer have been reported by some subsequent studies, although others have found incidence to be the same as in the general population. […] Antiretroviral therapy (ART) and highly active antiretroviral therapy (HAART) do not appear to have reduced cervical cancer incidence in women with HIV/AIDS and a systematic review found that the risk of invasive cervical cancer has increased since the introduction of HAART.
#25 16. Screening in immune-deficient women | Cancer Council
https://www.cancer.org.au/clinical-guidelines/cervical-cancer/cervical-cancer-screening/screening-in-immune-deficient-women
Cervical prevalence of oncogenic human papillomavirus (HPV) in HIV-positive women without cytological abnormalities is higher than their counterparts from the general population. […] HIV infection has been consistently associated with HPV infection and pre-cancerous cervical lesions, and a significantly higher rate of cervical cancer in women with HIV/acquired immune deficiency syndrome (AIDS) was reported in a meta-analysis of six population-based studies (incidence ratio: 5.8). […] High incidence rates of cervical cancer have been reported by some subsequent studies, although others have found incidence to be the same as in the general population. […] Antiretroviral therapy (ART) and highly active antiretroviral therapy (HAART) do not appear to have reduced cervical cancer incidence in women with HIV/AIDS and a systematic review found that the risk of invasive cervical cancer has increased since the introduction of HAART.
#26 16. Screening in immune-deficient women | Cancer Council
https://www.cancer.org.au/clinical-guidelines/cervical-cancer/cervical-cancer-screening/screening-in-immune-deficient-women
In solid organ transplant recipients, the majority of population-based studies have reported a higher incidence of cervical cancer than in their immunocompetent counterparts. […] There is also some evidence of a higher incidence of cervical intraepithelial neoplasia (CIN) in organ transplant recipients, although more research in this area is needed. […] The evidence regarding screening and treatment to prevent cervical cancer in immune-deficient women is of lower quality than that in the general population, due to the absence of long-term randomised controlled trials comparing screening strategies in these women. […] There is evidence of an increased risk of CIN in immune-deficient women, but evidence is also suggestive that screening plays an important role in reducing or removing excess risk of cervical cancer.
#27 16. Screening in immune-deficient women | Cancer Council
https://www.cancer.org.au/clinical-guidelines/cervical-cancer/cervical-cancer-screening/screening-in-immune-deficient-women
In solid organ transplant recipients, the majority of population-based studies have reported a higher incidence of cervical cancer than in their immunocompetent counterparts. […] There is also some evidence of a higher incidence of cervical intraepithelial neoplasia (CIN) in organ transplant recipients, although more research in this area is needed. […] The evidence regarding screening and treatment to prevent cervical cancer in immune-deficient women is of lower quality than that in the general population, due to the absence of long-term randomised controlled trials comparing screening strategies in these women. […] There is evidence of an increased risk of CIN in immune-deficient women, but evidence is also suggestive that screening plays an important role in reducing or removing excess risk of cervical cancer.
#28 16. Screening in immune-deficient women | Cancer Council
https://www.cancer.org.au/clinical-guidelines/cervical-cancer/cervical-cancer-screening/screening-in-immune-deficient-women
However, it is generally considered that the benefits outweigh the harms for immune-deficient women. […] The burden of HPV-related cancers can be expected to increase in HIV-positive women given successful prolongation of life with ART and potentially longer duration of HPV persistence. […] There is insufficient evidence available to determine the optimal cervical screening strategy in immune-deficient women.
#29 Long-term outcomes of high-risk human papillomavirus infection support a long interval of cervical cancer screening
https://pmc.ncbi.nlm.nih.gov/articles/PMC2266853/
Women who are HPV-negative bear little risk for CC in this study. This supports a focused cytology screening of HPV-infected women. In the current socio-economic setting in Taiwan, an HPV test-orientated screening is suggested. Only HPV-positive women have to be screened annually. Human papillomavirus-negative women may safely extend their screening interval to 5 years at least.
#30 Long-term outcomes of high-risk human papillomavirus infection support a long interval of cervical cancer screening | British Journal of Cancer
https://www.nature.com/articles/6604262
The cumulative risk for HSIL or above cervical neoplasia in HPV-positive subjects was 3.88% in 4 years, 4.88% in 5 years and 10.0% in 6 years. […] Women who are HPV-negative bear little risk for CC in this study. This supports a focused cytology screening of HPV-infected women. […] In the current socio-economic setting in Taiwan, an HPV test-orientated screening is suggested. Only HPV-positive women have to be screened annually. Human papillomavirus-negative women may safely extend their screening interval to 5 years at least.
#31 Long-term outcomes of high-risk human papillomavirus infection support a long interval of cervical cancer screening
https://pmc.ncbi.nlm.nih.gov/articles/PMC2266853/
Women who are HPV-negative bear little risk for CC in this study. This supports a focused cytology screening of HPV-infected women. In the current socio-economic setting in Taiwan, an HPV test-orientated screening is suggested. Only HPV-positive women have to be screened annually. Human papillomavirus-negative women may safely extend their screening interval to 5 years at least.
#32 HPV Status as Prognostic Biomarker in Head and Neck CancerâWhich Method Fits the Best for Outcome Prediction?
https://www.mdpi.com/2072-6694/13/18/4730
Despite clear tendencies of expression patterns when comparing the six different biomarkers with each other, a large gray zone was observed with ambiguous interpretation on the role of HPV in the individual tumor biology. […] A direct detection of HPV-DNA either using PCR or ISH can reliably be used as HPV surrogate biomarkers in OPSCC patients with substantial prognostic validity. […] The highly diverse expression patterns of HPV-related biomarkers reveal that there is only a low fraction of clearly HPV-positive and clearly HPV-negative head and neck cancers, with a large gray zone in between.
#33 Prediction of carcinogenic human papillomavirus types in cervical cancer from multiparametric magnetic resonance images with machine learning-based radiomics models – Diagnostic and Interventional Radiology
https://www.dirjournal.org/articles/prediction-of-carcinogenic-human-papillomavirus-types-in-cervical-cancer-from-multiparametric-magnetic-resonance-images-with-machine-learning-based-radiomics-models/doi/dir.2022.221335
In addition to the studies showing that HPV negativity before treatment is a poor prognostic factor for disease-free survival and overall survival, one study has shown that the carcinogenic HPV subtype has prognostic significance. […] The present study investigated the prediction of HPV status using pre-treatment MRI images. However, the changes in HPV status after treatment have also been shown to impact prognosis. Persistent HPV positivity in patients after radiotherapy is a poor prognostic factor. […] In conclusion, machine learning-based radiomics models based on pre-treatment MRI can detect carcinogenic HPV status with discriminative accuracy. The fact that HPV status, an essential prognostic factor in survival, can be predicted by MRI raises the issue of whether we can predict survival using MRI.
#34 HPV Status and Individual Characteristics of Human Papillomavirus Infection as Predictors for Clinical Outcome of Locally Advanced Cervical Cancer
https://www.mdpi.com/2075-4426/11/6/479
HPV status was determined in scrapings from the cervix of 173 CC patients before treatment. The tumors of 20 patients (11.5%) were HPV-negative for 14 high risk genotypes. HPV types 16 or 18 were detected in 115 patients (66.5%). A small proportion of HPV-negative tumors were found in almost all studies using highly sensitive HPV tests. Until now, the question of the existence of true HPV negative CC remains controversial. […] The presence of HPV 16/18 DNA integration of various degrees into the cell genome (integrated form) was found in the majority of patientsâin 66 cases (57.4%), of which 26 cases had complete (100%) integration of viral DNA. Absence of integration (episomal form) was registered in 49 (42.6%) patients. […] The study results served as the basis for combining patients with integrated HPV16/18 DNA (regardless of the degree of integration) and HPV-negative patients into one prognostic group. As a result of this combining, a single biomarker including HPV-negativity or presence of HPV16/18 DNA integration into the cell genome was created. In the general group of CC patients with stages IIâIII, OR of unfavorable outcome was several times higher in patients with presence of the biomarker than in other patients, and reached 8.9 (95% CI, 2.9â27.6; p = 0.0001) for period of 5 years.
#35 HPV Status and Individual Characteristics of Human Papillomavirus Infection as Predictors for Clinical Outcome of Locally Advanced Cervical Cancer
https://www.mdpi.com/2075-4426/11/6/479
Multivariate analysis included all variables regardless of statistical significance on univariate analysis: clinical and morphological characteristics (age, FIGO stage, histological type, nuclear grade, form of tumor growth, parametrial infiltration, metastases in lymph nodes, treatment method) and molecular genetic parameters of HPV infection (presence/absence of the biomarker, HPV genotype, number of genotypes, VL). As a result of multivariate analysis, three independent predictors of clinical outcome of locally advanced CC were identified: presence/absence of the biomarker (HPV-negative status or HPV16/18 DNA integration) (p = 1.2 Ã 10â4; OR = 9.67), stage of the disease (p = 0.001; OR = 4.69), age (p = 0.025; OR = 0.61). […] Thus, based on the results obtained, it is possible with high accuracy to predict clinical outcome (progression) of locally advanced cervical cancer according to the following criteria: HPV DNA status (negative/positive), physical state of HPV 16/18 DNA (episomal/integrated), stage of the disease, age. The application of our model in clinical practice makes it possible to identify CC patients with a high risk of disease progression in order to personalize treatment approaches in the future.