Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis

Abstract

Background Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely high-risk human papillomavirus (HPV) infection and cytohistopathology-predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer. MethodsWe did a systematic review of MEDLINE, Embase, and the Cochrane library for studies of cervical determinants of anal HPV and HSIL published up to Aug 31, 2018. We centrally reanalysed individual-level data from 13 427 women with paired cervical and anal samples from 36 studies. We compared anal high-risk HPV prevalence by HIV status, cervical high-risk HPV, cervical cytohistopathology, age, and their combinations, using prevalence ratios (PR) and 95% CIs. Among 3255 women with anal cytohistopathology results, PRs were similarly calculated for all anal HSIL and HPV16-positive anal HSIL. Findings Cervical and anal HPV infections were highly correlated. In HIV-negative women, anal HPV16 prevalence was 41% (447/1097) in cervical HPV16-positive versus 2% (214/8663) in cervical HPV16-negative women (PR 16•5, 95% CI 14•2-19•2, p<0•0001); these values were 46% (125/273) versus 11% (272/2588) in HIV-positive women (4•4, 3•7-5•3, p<0•0001). Anal HPV16 was also associated with cervical cytohistopathology, with a prevalence of 44% [101/228] for cervical cancer in HIV-negative women (PR vs normal cytology 14•1, 11•1-17•9, p<0•0001). Anal HSIL was associated with cervical high-risk HPV, both in HIV-negative women (from 2% [11/527] in cervical highrisk HPV-negative women up to 24% [33/138] in cervical HPV16-positive women; PR 12•9, 95% CI 6•7-24•8, p<0•0001) and HIV-positive women (from 8% [84/1094] to 17% [31/186]; 2•3, 1•6-3•4, p<0•0001). Anal HSIL was also associated with cervical cytohistopathology, both in HIV-negative women (from 1% [5/498] in normal cytology up to 22% [59/273] in cervical HSIL; PR 23•1, 9•4-57•0, p<0•0001) and HIV-positive women (from 7% [105/1421] to 25% [25/101]; 3•6, 2•5-5•3, p<0•0001). Prevalence of HPV16-positive anal HSIL was 23-25% in cervical HPV16-positive women older than 45 years (5/20 in HIV-negative women, 12/52 in HIV-positive women).Interpretation HPV-based cervical cancer screening programmes might help to stratify anal cancer risk, irrespective of HIV status. For targeted secondary anal cancer prevention in high-risk groups, HIV-negative women with cervical HPV16, especially those older than 45 years, have a similar anal cancer risk profile to that of HIV-positive women.

Association of antiretroviral therapy with anal high-risk human papillomavirus, anal intraepithelial neoplasia, and anal cancer in people living with HIV: a systematic review and meta-analysis

“…Interestingly, there was a high prevalence of anal HR-HPV reported, accompanied with high prevalence of HSIL-AIN2+ in these populations. For women and MSW, there could be a difference in risk of anal lesions if infected through auto-inoculation or passive migration, (84) and for women via sexual transmission route. A small proportion of MSW reported ever practicing RAI, although we also cannot rule out the possibility that studies among MSW may have misreported or underreported history of RAI.…”

A meta‐analysis of anal cancer incidence by risk group: Toward a unified anal cancer risk scale

“…Important population‐level determinants of anal cancer incidence include age (via accumulation of deleterious mutations) and female gender (genital/anal anatomical proximity favoring HPV cross‐site transmission) 5 . However, anal cancer risk is also heavily driven by sexual behavior, 6 and by immunosuppression, 7 which worsens the carcinogenic outcome of anal HPV infection.…”

Sequential Acquisition of Human Papillomavirus Infection at Genital and Anal Sites, Liuzhou, China

“…These facts imply that other modes of transmission, independent of penile-anal penetration, are possible for acquiring anal HPV infections. Recently, Lin et al (8) conducted a collaborative pooled analysis in paired cervical and anal samples and found a strong association between the presence of high-risk HPV (HR-HPV) at these 2 sites at the type-specific level, suggesting having the same source of infection either from the same sexual partner, autoinoculation within different anogenital sites, or both.…”