Age-Specific Prevalence of Anal and Cervical Human Papillomavirus Infection and High-Grade Lesions in 11 177 Women by Human Immunodeficiency Virus Status: A Collaborative Pooled Analysis of 26 Studies

Abstract

Background Age-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention. Methods We centrally re-analyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by HIV status and age. For women living with HIV (WLWH) with anal high-grade squamous intraepithelial lesions (HSIL+), we also investigated concurrent cervical cytopathology. Results In HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15-24 years to 1.0% at ≥55 years; ptrend=0.0026) and cervix (7.4% to 1.7%; <0.0001). In WLWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; 0.0035), but not anus (11.5% to 13.9%; 0.5412). Given anal HPV16-positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend=0.0005) and WLWH (0.0166). Among 48 WLWH with HPV16-positive anal HSIL+, 27(56%) were cervical HR-HPV-positive, including 8 with cervical HPV16, and 5 with cervical HSIL+. Conclusions Age-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WLWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk.

A systematic review and meta‐analysis of cytology and HPV‐related biomarkers for anal cancer screening among different risk groups

“…There is accumulating evidence that some biomarkers, like HPV16, could stratify the heterogeneous group of AIN2/3 into those that are more or less likely to progress to cancer. 2,57 Similarly, other biomarkers such as p16/Ki-67 and methylation could be considered to improve anal disease classification in future analyses. A second limitation of this study is that due to the urgency of generating evidence for ongoing guidelines efforts, we did not obtain individual-level data from studies which would allow to evaluate more test combinations such as anal cytology and HPV16/18 genotyping.…”

“…Similar to CIN2 in cervical cancer screening, AIN2 is a poorly reproducible, heterogenous disease category, whereas AIN3 is likely a better surrogate of anal cancer risk. There is accumulating evidence that some biomarkers, like HPV16, could stratify the heterogeneous group of AIN2/3 into those that are more or less likely to progress to cancer 2,57 . Similarly, other biomarkers such as p16/Ki‐67 and methylation could be considered to improve anal disease classification in future analyses.…”

Anal Intraepithelial Neoplasia and Anal Squamous Cell Carcinoma: Updates From the Last 3 Years

“…11 In contrast to cervical HPV16 prevalence, which declined with age, the anal HPV16 prevalence was constant with aging. 11 The number of studies describing the prevalence of anal HPV infection and anal HSIL in solid organ transplant recipients is much lower than the number of such studies in people living with HIV. A meta-analysis showed that the prevalence of HPV16 was 4% and that of anal HSIL was 5% (approximately 4 times lower than in MSM living with HIV).…”

“…Regarding HPV clearance in men, another large study (a pooled analysis of 34 longitudinal studies) confirmed that the clearance of HPV16 was lower for people living with HIV 10 . A pooled analysis of 26 studies showed that in women living with HIV, the prevalence of anal HPV16 was 12%, higher than in the cervix (9%), and the prevalence of anal HSIL was 6% 11 . In contrast to cervical HPV16 prevalence, which declined with age, the anal HPV16 prevalence was constant with aging 11 …”

“…A pooled analysis of 26 studies showed that in women living with HIV, the prevalence of anal HPV16 was 12%, higher than in the cervix (9%), and the prevalence of anal HSIL was 6% 11 . In contrast to cervical HPV16 prevalence, which declined with age, the anal HPV16 prevalence was constant with aging 11 …”