Cancer Burden Attributable To HPV And Cervical Cancer Screening In Women Living With HIV In China

ObjectivesTo estimate burden and temporal trend of cancer attributable to HPV infection in China,provide scientific data for HPV vaccination and cancer prevention.To explore the prevalence and risk factors for anogenital HPV infection and neoplasia,and evaluate the clinical performance of LBC,HPV tests,and VIA/VILI as primary screening and triage programs,among women living with HIV(WLHIV)in China.Materials and methods1.HPV related cancer incidence and mortality from 2007 to 2015 were extracted from Chinese cancer registry annual report,the national population were from National Bureau of Statistics.HPV-attributable cancer burden was estimated by incorporating cancer rates,population forecasts and corresponding population attributable fractions(PAF)by sex,geographical area,and age.Temporal trend and prediction of cancer burden were estimated.2.From 2019 to 2020,409 WLHIV aged 18 years and older were recruited from an HIV treatment clinic in Yunnan,China.After collecting sociodemographic and HIV related characteristics,women underwent:self-sampling for HPV testing,physician-sampling and anal sampling for HPV testing and cytological interpretation,and VIA/VILI.Women positive for cervical HPV or cytological abnormalities were recalled for colposcopy examination and biopsy when necessary.Prevalence and risk factors for anogenital HPV infection and neoplasia were compared;The clinical performance of LBC,HPV tests,and VIA/VILI were evaluated for detecting CIN2+/CIN3+.Results1.It estimated that 113558 HPV-attributable new cancer cases in China in 2015,including 102397(90.2%)cervical cancers and 11161(9.8%)non-cervical cancers.Of those,106611(93.9%)cancers in females including 4214 non-cervical cancers,and 6947(6.1%)cancers in males.Age-standardized incidence was 5.83 per 100000 persons,10.97 for females and 0.71 for males,5.58 in urban and 6.14 in rural.Among females,49.3%of new cancers were diagnosed in women aged 40-54 years,while 59.0%of non-cervical cancers were diagnosed in 50-74 years.Among males,55.9%of cancers were diagnosed in men aged 55-74 years.The cancer incidence increases with age,reaching a peak at the age of 50-54 years and then decreasing slowly among females.The incidence of non-cervical cancer in females and males increases gradually with age.36920 HPV-attributable cancer deaths were estimated,including 31125(84.3%)due to cervical cancer and 5795(15.7%)non-cervical cancer,33192(89.9%)in females(2067 non-cervical cancer deaths),and 3728(10.1%)in males.Age-standardized mortality was 1.83 per 100000 persons,3.27 for females and 0.37 for males.From 2007 to 2015,cancer cases attributable to HPV infection were increased by 3.8%(95%CI:2.9-4.8)per year,and the incidence as well(AAPC 3.0%,95%CI:2.5-3.5).HPV-attributable cancer deaths(AAPC 4.7,95%CI:2.9-6.7)and mortality(3.3,0.9-5.8)showed an upward trend.From 2016 to 2025,the predicted HPV-attributable cancer cases increase from 117846 to 171579,with the incidence rising from 6.13 to 8.18 per 100,000 persons.In 2025,cervical cancer(152356)contributed 90%of new cancer cases attributable to HPV with the incidence of 14.87 per 100000 persons,followed with anal cancer(8955 cases,0.33 per 100,000 persons).2.HPV prevalence was 34.2%for cervical and 34.7%for anal(HR-HPV being 30.6%and 30.3%,respectively)among WLHIV in Yunnan.The most frequent genotypes were HPV-52,16,58 in the cervix,HPV-52,53 and 39 in the anus,with the strong correlation between cervical and anal positivity,both overall(OR=3.48,95%CI=2.26-5.36)and at a type-specific level(e.g.HPV-16,OR=6.61,95%CI=2.17-20.17).Cervical HR-HPV infection was most associated with short-duration of combination antiretroviral therapies(ART)(≤2 vs>2 years,aOR=2.25,95%CI=1.22-4.12),and high initial HIV viral load(≥1000 vs<1000 CPs/mL,aOR=1.98,95%CI=1.10-3.58).Prevalence of anal HPV was higher among women with low nadir CD4 count(<200 vs ≥200 cells/μL,aOR=1.80,95%CI=1.01-3.22)and low current CD4 count(<350 vs≥500 cells/μL,aOR=2.06,95%CI=1.00-4.36).CIN2+prevalence was 4.6%and associated with low nadir CD4 count(aOR=4.63,95%CI=1.24-17.25).3.Among WLHIV,HPV tests detected more CIN2+cases compared to LBC while VIA/VILI had a similar detection rate.Sensitivity and specificity were approximately 90%(HC2:100%,cobas:89.5%,Sansure HPV:100%)and more than 70%(HC2:80.4%,cobas:85.1%,Sansure HPV:72.0%)for physician-HPV tests,61.1%and 96.3%for LBC(ASCUS+),40.0%and 77.3%for VIA/VILI,concurrently with the AUC around 0.90(HC2:0.90,cobas:0.87,Sansure HPV:0.86),0.79,0.59 respectively for detecting CIN2+.Self-HPV test achieved considerable performance with physician-HPV At CIN2 threshold,triaging HPV-positive women with LBC(ASCUS+),HPV-16/18 genotyping,and VIA/VILI elevated specificity with declined sensitivity.HPV-16/18/31/3 3/45/5 2/58 genotyping demonstrated the optimal accuracy(89.5%sensitivity,81.9%specificity,0.86 AUC)as a triage method,and was similar to the HPV-16/18 with reflex LBC(ASCUS+).ART ≤2 years was associated with decreased specificity of Hybrid Capture 2(aOR=1.87,95%CI=1.22-3.91)and Sansure HPV(2.48,1.43-4.29).ConclusionsThe cancer burden attributable to HPV in China is substantial,with increasing cancer cases and deaths in past nearly 10 years and future 10 years,cervical cancer was the highest burden,while anal cancer was the highest burden among non-cervical cancers.HPV vaccination and cervical cancer screening should be prioritized.While anogenital cancer screening or HPV vaccination could be provided among high-risk population like HIV infected individuals.Cervical and anal HPV were strongly correlated and,together with associated neoplasia,were highly prevalent among WLHIV in Yunnan,China.Early initiation of ART to avoid severe immunodeficiency would decrease anogenital HPV prevalence and related cancer burden among WLHIV.Incorporating anogenital cancer prevention services into HIV/AIDS care is warranted.For cervical cancer screening in WLHIV,LBC,or HPV test alone as primary screening methods,or HPV with triage demonstrated satisfactory clinical performance.Self-HPV tests followed by the restricted HR-HPV genotyping triage within one test is highly recommended to be incorporated into HIV/AIDS care.Optimal triage to increase the HPV specificity among women with short-duration of ART is needed.