Human papillomavirus types from infection to cancer in the anus, according to sex and HIV status: a systematic review and meta-analysis

Abstract

SummaryBackgroundData on carcinogenicity of human papillomavirus (HPV) types in the anus are needed to inform anal cancer prevention through vaccination and screening. This is particularly the case for people infected with HIV, who are at an increased risk of anal cancer.MethodsWe did a systematic review of studies published from January, 1986, to July, 2017, in MEDLINE, Embase, and the Cochrane Library on anal HPV infection, without any language restrictions. Eligible studies reported type-specific HPV prevalence by strata of cytopathological or histopathological anal diagnosis, sex, and HIV status. Data requests were made to authors when necessary. We did a meta-analysis of type-specific HPV prevalence across the full spectrum of anal diagnoses, from normal cytology to anal cancer. We assessed the main outcome of type-specific HPV prevalence ratios [PR], calculated across strata of anal diagnoses, gender, or HIV status, by use of generalised linear models.Findings95 studies were identified from the search, published between 1992–2017, from which 18 646 individuals fulfilled the criteria for inclusion in the analyses: 8534 people with normal cytology, 5730 with low-grade lesions, 2024 with high-grade lesions, and 2358 with anal cancer. HPV prevalence varied in normal cytology from 42% in HIV-negative women to 76% in HIV-positive men and, for each diagnosis, was higher in individuals who were HIV positive than those who were HIV negative. HPV16 positivity increased with diagnosis severity, being the only HPV type accounting for more HPV infection in anal cancer than normal cytology, both in individuals who were HIV negative (PR 5·0, 95% CI 3·8–6·6, p<0·0001) and those who were HIV positive (2·3, 1·9–2·7, p<0·0001). HPV16 positivity increased even between high-grade lesions and anal cancer, whereas other high-risk HPV types accounted for high proportions of low-grade or high-grade lesions but their prevalence decreased in anal cancer. However, HPV16 was less frequent in HIV-positive than HIV-negative anal cancer, both in men (PR 0·8, 95% CI 0·7–0·9, p<0·0001) and women (0·8, 0·6–1·0, p=0·063), and in HIV-positive versus HIV-negative high-grade lesions in women (0·6, 0·5–0·9, p=0·0077). Type-specific attribution of the non-HPV16 fraction of HIV-positive anal cancer is hindered by a high prevalence of multiple HPV infections.InterpretationHPV16 is by far the most carcinogenic HPV type in the anus, with enrichment of HPV16 even from high-grade lesions to anal cancer, both in individuals who are HIV negative and those who are HIV positive. Nevertheless, the fraction of anal cancer attributable to HPV16 is smaller in the HIV-positive population.FundingInternational Agency for Research on Cancer.

Electrocautery ablation of anal high‐grade squamous intraepithelial lesions: Effectiveness and key factors associated with outcomes

“…We recently reported that baseline HPV‐16 and/or HPV‐18 infection was associated with an increased likelihood of progression from anal low‐grade squamous intraepithelial lesion to HSIL compared with baseline infection with non–HPV‐16 and/or HPV‐18 high‐risk HPV types . Taken together, the findings of the current study underscore the importance of HPV‐16 and HPV‐18 in anal carcinogenesis, suggesting a potential role for HPV genotyping for risk stratification in anal cancer screening . Studying the role of high‐risk HPV infection and HIV‐related local immune disturbance in the continuum of disease progression, screening effectiveness, HSIL treatment, and continued surveillance may help to formulate more targeted anal cancer prevention algorithms that will maximize the value of screen‐and‐treat approaches.…”

Anal cytological lesions and HPV infection in individuals at increased risk for anal cancer

“…We also found that the detection of HPV‐16/18, the most prevalent genotypes in anal cancer, increased with the severity of the cytological lesions in both study groups, and there was a peak in HSILs, which were HPV‐16/18–positive in 50% to 67% of the cases. Interestingly, a recent meta‐analysis showed that only the prevalence of HPV‐16, in comparison with other HR types, increased significantly with the anal lesion grade on cytology in both HIV‐negative and HIV‐positive individuals . In the latter group, the HPV‐16 prevalence increased from 26% in subjects with negative cytology to 51% in those with HSILs.…”

Strategies for screening and early detection of anal cancers: A narrative and systematic review and meta‐analysis of cytology, HPV testing, and other biomarkers

“…C,D), and diagnosis of anal cancer peaks from approximately ages 45 to 64 years . Among those with normal anal cytology, HPV prevalence is approximately 42% and 59% in HIV‐negative and HIV‐positive women, respectively, and 57% and 76% in HIV‐negative and HIV‐positive men, respectively . In contrast, in HIV‐negative men who have sex with women, HPV prevalence is much lower (6%).…”