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. 2023 Feb 14;227(4):488-497.
doi: 10.1093/infdis/jiac108.

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

Feixue Wei  1 , Ningshao Xia  2 , Rebeca Ocampo  3 , Marc T Goodman  4 , Nancy A Hessol  5   6 , Beatriz Grinsztejn  7 , Ana P Ortiz  8   9 , Fanghui Zhao  10 , Erna M Kojic  11 , Rupert Kaul  12 , Isabelle Heard  13 , Imran O Morhason-Bello  14   15 , Anna-Barbara Moscicki  16 , Alexandra de Pokomandy  17 , Joel M Palefsky  6 , Luana L S Rodrigues  18   19 , Racheal S Dube Mandishora  1   20 , Reshmie A Ramautarsing  21 , Silvia Franceschi  22 , Sheela V Godbole  23 , Fernanda K Tso  24 , Lynette J Menezes  25 , Chunqing Lin  26 , Gary M Clifford  1
Affiliations

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

Feixue Wei et al. J Infect Dis. .

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 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.

Keywords: HIV; HPV; anus; cervix; women.

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Conflict of interest statement

Potential conflicts of interest. A. P. O. reports grants made to her institutions from AMC, grant no. 2UM1CA121947 and an UPR/MDACC Partnership grant no. 2U54CA096297 for time and effort support to the present manuscript. She reports NIH grants not related to the current work. She reports consulting fees and payment for lectures from Merck and Co. R. K. was supported by the Canadian Institutes of Health Research (CIHR) for the present manuscript. A. d. P. shared data from the EVVA study for this manuscript. The EVVA study was supported by the CIHR, and the AIDS and Infectious Diseases Network of Fonds de Recherche du Quebec Sante. Payments were made to A. d. P.’s institution. J. M. P. reports grants and personal fees from Merck and Co.; consulting fees from Vir Biotechnology, Antiva Biosciences, and Virion Therapeutics; personal fees Janssen Pharmaceuticals; stock or stock options from Virion Therapeutics and Vir Biotechnology (outside the submitted work); and a leadership role in the International Papillomavirus Society. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Overall prevalence of anal and cervical human papillomavirus (HPV) infection in (A) human immunodeficiency virus (HIV)-negative women and (B) women with HIV. Error bar = 95% confidence interval. *Indicated HPV prevalence was statistically significantly different in the anus and the cervix using χ2 test. 2v-HPV, HPV16 and 18; 4v-HPV, HPV6, 11, 16, and 18; 9v-HPV, HPV6, 11, 16, 18, 31, 33, 45, 52, and 58; HR-HPV, high-risk HPV; HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68.
Figure 2.
Figure 2.
Age-specific prevalence of anal and cervical human papillomavirus (HPV)16 and high-risk (HR)-HPV infection in human immunodeficiency virus (HIV)-negative women and women with HIV: (A) HPV16 prevalence in HIV-negative women; (B) HPV16 prevalence in women with HIV; (C) HR-HPV prevalence in HIV-negative women; (D) HR-HPV prevalence in women with HIV. Error bar = 95% confidence interval. Significant prevalence ratios (PRs) relative to the reference group are shown in bold. HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68.
Figure 3.
Figure 3.
Combination of age-specific cervical and anal human papillomavirus (HPV)16 prevalence in (A) human immunodeficiency virus (HIV)-negative women and (B) women with HIV. *Concurrent cervical HPV16 infection in all women with anal HPV16 infection by age group.
Figure 4.
Figure 4.
Overall and age-specific multiplicity of high-risk human papillomavirus (HPV) infection in women by human immunodeficiency virus (HIV) status and anatomic site: (A) anal HPV infection in HIV-negative women; (B) cervical HPV infection in HIV-negative women; (C) anal HPV infection in women with HIV; (D) cervical HPV infection in women with HIV.
Figure 5.
Figure 5.
Comparison of age-specific prevalence of anal (A) human papillomavirus (HPV)16 and (B) high-risk (HR) HPV infection among women (in this study) and men [7], according to human immunodeficiency virus (HIV) status and male sexuality. HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68; MSM, men who have sex with men; MSW, men who have sex with women.
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