Incidence and Clearance of Anal Human Papillomavirus Infection in 16 164 Individuals, According to Human Immunodeficiency Virus Status, Sex, and Male Sexuality: An International Pooled Analysis of 34 Longitudinal Studies

Abstract

Background Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programmes but has not been systematically characterised. Methods We reanalysed data from 34 studies with 16 164 individuals in six risk groups defined by HIV status, gender, and male sexuality: men who have sex with men (MSM) living with HIV (LWH) [MSMLWH], HIV-negative MSM, women LWH (WLWH), HIV-negative women, men who have sex with women (MSW) LWH (MSWLWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants. Results HPV16 had the highest incidence:clearance ratio of the hrHPV types. MSMLWH had highest hrHPV incidence (e.g. 15.5% newly HPV16-infected within two years), followed by HIV-negative MSM (7.5%), WLWH (6.6%), HIV-negative women (2.9%), MSWLWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behaviour for MSM only. HPV16 clearance was lower for people LWH (PLWH), and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV16 infection. Conclusions This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programmes on anal cancer prevention, particularly in MSM and PLWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.

Incidence of abnormal anal cytology in HIV‐infected and HIV‐uninfected men who have sex with men

“…This might be surprising given that HIV-infected subjects are more likely to harbor anal HPV and HPVrelated lesions 2,7 and display higher incidence and lower clearance rates of high-risk types compared with the HIV-uninfected counterparts. 24 However, HIV-uninfected and HIV-infected MSM of our study displayed major differences in terms of age and sexual exposure. HIV-uninfected MSM were significantly younger and displayed a higher sexual exposure (more lifetime and recent partners, more likely to have casual partners) than the HIV-infected counterparts.…”

“…Interestingly, our study showed no significant differences between the two groups. This might be surprising given that HIV‐infected subjects are more likely to harbor anal HPV and HPV‐related lesions 2,7 and display higher incidence and lower clearance rates of high‐risk types compared with the HIV‐uninfected counterparts 24 . However, HIV‐uninfected and HIV‐infected MSM of our study displayed major differences in terms of age and sexual exposure.…”

“…Notably, the strongest independent predictor of ASC‐US+ incidence in our study was represented by condomless receptive anal intercourse. This is an important concept, given that more than 80% of approximately 6000 HIV‐infected and HIV‐uninfected MSM reported engaging in receptive anal sex 24 . In addition, our study showed that approximately 40% of those engaging in this sexual practice do not use a condom.…”

“…These may be either longstanding or recently acquired infections. Importantly, it has been observed that incident anal infections are cleared in a relatively short time compared with prevalent infections 24 ; therefore, incident infections will not likely lead to the development of cytological abnormalities. Notably, the occurrence of abnormal cytology significantly differed according to high‐risk HPV persistence both among HIV‐uninfected and HIV‐infected MSM.…”

“…In addition, our study showed that approximately 40% of those engaging in this sexual practice do not use a condom. Receptive anal sex has been identified as a risk factor for acquisition of anal HPV infection in HIV‐uninfected MSM, 14 and HPV16 in HIV‐infected and HIV‐uninfected MSM, 24 although condom use was not taken into account.…”