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Background We sought to summarize human papillomavirus (HPV) vaccine efficacy/effectiveness (VE) against anal HPV infection and anal intraepithelial neoplasia (AIN). Methods We performed literature review and meta-analysis to estimate VE, stratified by age and analytic population (per-protocol efficacy [PPE] or intention-to-treat [ITT] population in clinical trials, or all participants in real-world studies). Results We identified 6 clinical trials and 8 real-world studies. In participants vaccinated at age ≤26 years (mainly human immunodeficiency virus [HIV]–negative individuals), significant VE against incident/prevalent anal HPV infection was reported in clinical trials, with a higher estimate in PPE (2 studies with 2390 participants; VE, 84% [95% confidence interval (CI), 77%–90%]; I 2 = 0%) than ITT (2 studies with 4885 participants; 55%, 39%–67%; I 2 = 46%) populations or in real-world studies (4 studies with 2375 participants; 77%, 40%–91%; I 2 = 81%). HPV vaccination at age ≤26 years was associated with significant VE in preventing persistent anal HPV infection and AIN. No significant VE against anal HPV infection or AIN was found in persons vaccinated at age >26 years (mainly people living with HIV). Conclusions There is strong evidence for high VE against anal HPV infection and AIN in HIV-negative individuals vaccinated at age ≤26 years. However, the lower impact in ITT than in PPE populations and the lack of significant effect in people living with HIV aged >26 years indicates that vaccines have the higher impact in populations with less sexual exposure to anal HPV. [ABSTRACT FROM AUTHOR]

Background Age-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention. Methods We centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (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%; ptrend < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; ptrend = 0.0035) but not anus (11.5% to 13.9%; ptrend = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend = 0.0005) and WWH (ptrend = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were 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 WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk. [ABSTRACT FROM AUTHOR]

Background Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized. Methods We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants. Results Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 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 programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection. [ABSTRACT FROM AUTHOR]

Background Human papillomavirus (HPV) causes anogenital warts and cancers in men and women. However, little is known about sex differences regarding the natural history of anogenital HPV infection. Methods Starting in May 2014, an observational cohort study including 2309 men and 2378 women aged 18–55 years was conducted in Liuzhou, China. Samples from anogenital sites were tested for HPV genotypes by multicolor real-time polymerase chain reaction and melting curve analysis biannually for ~1 year. Results The incidence of oncogenic HPV infection was similar in men and women (10.3 and 11.5/1000 person-months; P =.275), whereas the incidence of HPV-6/11 infection was higher in men than in women (2.0 vs 1.1; P =.018). The incidence of both oncogenic HPV and HPV-6/11 infections was significantly higher in women in the 18- to 25-year age group than in the older age groups (P =.006 and.011, respectively), whereas it did not vary by age among men (P =.552 and.425, respectively). Additionally, men were more likely than women to clear oncogenic infections (101.5 vs 58.6/1000 person-months; P <.001), but no significant difference was found in the clearance of HPV-6/11 by sex (111.7 vs 84.8; P =.266). The median time to clearance of oncogenic type and type 6/11 infections was not age dependent for either sex (all P >.05). Conclusions The natural history of oncogenic and nononcogenic HPV infection differs by sex, which implies that sex-specific vaccination strategies should be considered for oncogenic and nononcogenic HPV. Clinical Trials Registration NCT02188004. [ABSTRACT FROM AUTHOR]

Background: Knowledge of human papillomavirus (HPV) transmission dynamics, which have important public health implications for designing HPV vaccination strategies, is scarce in undeveloped areas.Methods: From May to July 2014, 390 couples were enrolled from the general population in Liuzhou, China. Exfoliated cells from male penis shaft/glans penis/coronary sulcus (PGC) and perianal/anal canal (PA) sites and from female vaginal, vulvar, and PA sites were collected biannually for 1 year.Results: The HPV type-specific concordance rate between couples was 15.5% (95% confidence interval [CI], 8.5%-25.0%). For anogenital HPV transmission, the male-to-female transmission rate (11.5 [95% CI, 4.3-30.7] per 1000 person-months) was similar to the female-to-male transmission rate (11.3 [95% CI, 5.9-21.7] per 1000 person-months). The concordance rates between male PGC site and female vaginal, vulvar, and PA sites were 20.0%, 21.8%, and 14.9%, respectively, which were significantly higher than expected by chance. Infections transmitted from males to females seemed mainly originated from male genital sites, whereas for female-to-male transmission, the vaginal, vulvar, and PA sites might be all involved.Conclusions: Among the heterosexual couples with relatively conservative sexual behavior, the anogenital HPV transmission rate for females to males is similar to that of males to females. In addition to the vagina and vulva, the female PA site is also an important reservoir for HPV transmission. [ABSTRACT FROM AUTHOR]

Anal cancer is primarily caused by human papillomavirus (HPV) infection in both men and women. However, little is known about the sex differences in the natural history of anal HPV infection in a heterosexual population. From May 2014 to March 2016, perianal/anal canal (PA) swab samples were collected semiannually from 2,302 heterosexual men and 2,371 heterosexual women aged 18–55 years old in Liuzhou, China. The specimens were genotyped for HPV DNA by polymerase chain reaction. The incidence rate ratio (IRR) and clearance rate ratio (CRR) were used to analyze the sex differences of incidence and clearance by Poisson regression, respectively. The incidences of PA oncogenic HPV in men and women were 3.4 per 1,000 person‐months and 8.6 per 1,000 person‐months, respectively, with an IRR of 0.39 (95% confidence interval (CI), 0.29–0.54 for men versus women) (p < 0.0001). The CRR of PA oncogenic HPV infection for men versus women was 1.54 (95% CI, 1.17–2.03) (p = 0.0022). At 12 months, 44% (20/45) of HPV 16/18 infections among women remained positive, whereas no (0/7) infections persisted among men (p = 0.0350). Both the higher incidence and slower clearance of anal carcinogenic HPV infection among women may lead to a higher burden of anal cancer among women than among men in a heterosexual population. What's new? While human papillomavirus (HPV) infection is a major cause of anal cancer in men and women, anal cancer incidence differs between the sexes. The dynamics of anal HPV infection in the general heterosexual population, however, are not well understood. Here, women were found to have a higher risk of acquiring anal carcinogenic HPV infection than men based on follow‐up and analysis of perianal/anal canal specimens for approximately 4,000 heterosexual Chinese men and women. Women were also found to have a lower likelihood of clearing anal HPV infection. These differences potentially contribute to increased anal cancer burden in women. [ABSTRACT FROM AUTHOR]

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.Methods: We 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 high-risk 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.Funding: International Agency for Research on Cancer. [ABSTRACT FROM AUTHOR]