Prevalent, persistent anal HPV infection and squamous intraepithelial lesions: Findings from a cohort of men living with HIV in South Africa

Autoři: Admire Chikandiwa aff001;  Pedro. T. Pisa aff001;  Catherine Tamalet aff002;  Etienne. E. Muller aff003;  Pamela Michelow aff004;  Matthew. F. Chersich aff001;  Philippe Mayaud aff001;  Sinead Delany-Moretlwe aff001
Působiště autorů: Wits RHI, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa aff001;  Department of Clinical Microbiology IHU and CNRS-URMITE, UMR 7278 Timone University Hospital Marseille, France aff002;  National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa aff003;  Cytology Unit, Department of Anatomical Pathology, University of the Witwatersrand and National Health Laboratory Services, Johannesburg, South Africa aff004;  London School of Hygiene and Tropical Medicine, London, United Kingdom aff005
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article



To estimate the prevalence, incidence and persistence of anal HPV infection and squamous intra-epithelial lesions (SILs) among men living with HIV (MLHIV), and determine their risk factors.


We enrolled MLHIV ≥18 years, who attended 6-monthly visits for 18 months. Socio-behavioural data were collected by questionnaire. Clinicians collected blood sample (CD4+ count and HIV plasma viral load), anal swabs (HPV DNA testing) and anal smears (Bethesda classification) at each visit. HPV DNA testing and classification of smears were done at enrolment and last follow-up visit (two time points). Factors associated with persistent anal HPV infection and SILs were evaluated with generalized estimating equations logistic regression and standard logistic regression respectively.


Mean age of 304 participants was 38 (Standard Deviation, 8) years; 25% reported >1 sexual partner in the past 3 months. Only 5% reported ever having sex with other men. Most (65%) participants were taking antiretroviral treatment (ART), with a median CD4+ count of 445 cells/μL (IQR, 328–567). Prevalence of any-HPV infection at enrolment was 39% (88/227). In total, 226 men had anal HPV DNA results at both enrolment and final visits. Persistence of any-anal HPV infection among 80 men who had infection at enrolment was 26% (21/80). Any persistent anal HPV infection was more frequent among MLHIV with low CD4+ count (<200 vs. >500 cells/μL; aOR = 6.58; 95%CI: 2.41–17.94). Prevalence of anal SILs at enrolment was 49% (118/242) while incidence of SILs among MLHIV who had no anal dysplasia at enrolment was 27% (34/124). Of the 118 men who had anal dysplasia at enrolment, 15% had regressed and 38% persisted by month 18. Persistent anal HPV infection was associated with persistent SILs (aOR = 2.95; 95%CI: 1.08–10.89). ART status or duration at enrolment were not associated with persistent anal HPV infection or persistent SILs during follow-up.


In spite of a high prevalence of anal HPV, HIV-positive heterosexual men have a low burden of anal HPV related disease. HPV vaccine and effective ART with immunological reconstitution could reduce this burden of infection.

Klíčová slova:

Cell enumeration techniques – Cytology – Dysplasia – Human papillomavirus – Human papillomavirus infection – Infectious disease control


1. Schiffman M, Castle PE. Human papillomavirus: epidemiology and public health. Archives of pathology & laboratory medicine. 2003;127(8):930–4. Epub 2003/07/23. doi: 10.1043/1543-2165(2003)127<930:hpeaph>;2 12873163.

2. de Martel C, Plummer M, Vignat J, Franceschi S. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 2017. Epub 2017/04/04. doi: 10.1002/ijc.30716 28369882.

3. Chin-Hong PV, Palefsky JM. Natural history and clinical management of anal human papillomavirus disease in men and women infected with human immunodeficiency virus. Clin Infect Dis. 2002;35(9):1127–34. doi: 10.1086/344057 12384848

4. Delany-Moretlwe S, Chikandiwa A, Gibbs J. Human papillomavirus infection and disease in men: Impact of HIV. Southern African Journal of HIV Medicine. 2013;14(4):183–8.

5. Beachler DC, Sugar EA, Margolick JB, Weber KM, Strickler HD, Wiley DJ, et al. Risk factors for acquisition and clearance of oral human papillomavirus infection among HIV-infected and HIV-uninfected adults. Am J Epidemiol. 2015;181(1):40–53. Epub 2014/12/07. doi: 10.1093/aje/kwu247 25480823

6. Shiels MS, Pfeiffer RM, Chaturvedi AK, Kreimer AR, Engels EA. Impact of the HIV Epidemic on the Incidence Rates of Anal Cancer in the United States. JNCI 2012;104(20):1591–8. doi: 10.1093/jnci/djs371 23042932

7. Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ. Natural innate and adaptive immunity to cancer. Annu Rev Immunol. 2011;29:235–71. Epub 2011/01/12. doi: 10.1146/annurev-immunol-031210-101324 21219185.

8. zur Hausen H. Papillomaviruses in the causation of human cancers—a brief historical account. Virology. 2009;384(2):260–5. Epub 2009/01/13. doi: 10.1016/j.virol.2008.11.046 19135222.

9. Schiffman M, Castle PE, Jeronimo RJ, Rodrigue AC, Wacholder S. Human papillomavirus andcervica lcancer. Lancet. 2007;370(9590):890–907. doi: 10.1016/S0140-6736(07)61416-0 17826171

10. Stanley MA, Winder DM, Sterling JC, Goon PKC. HPV infection, anal intra-epithelial neoplasia (AIN) and anal cancer: current issues. BMC cancer. 2012;12:398-. doi: 10.1186/1471-2407-12-398 22958276.

11. Machalek DA, Poynten M, Jin F, Fairley CK, Farnsworth A, Garland SM, et al. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol. 2012;13(5):487–500. doi: 10.1016/S1470-2045(12)70080-3 22445259

12. Segondy M, Ngou J, Kelly H, Omar T, Goumbri-Lompo O, Doutre S, et al. Diagnostic value of human papillomavirus (HPV) 16 and HPV18 viral loads for the detection of high-grade cervical intraepithelial neoplasia (CIN2+) in a cohort of African women living with HIV. J Clin Virol. 2018;99–100:79–83. Epub 2018/01/22. doi: 10.1016/j.jcv.2018.01.006 29353074.

13. Kelly H, Weiss HA, Benavente Y, de Sanjose S, Mayaud P. Association of antiretroviral therapy with high-risk human papillomavirus, cervical intraepithelial neoplasia, and invasive cervical cancer in women living with HIV: a systematic review and meta-analysis. The lancet HIV. 2018;5(1):e45–e58. Epub 2017/11/07. doi: 10.1016/S2352-3018(17)30149-2 29107561

14. Wilkin TJ, Palmer S, Brudney KF, Chiasson MA, Wright TC. Anal intraepithelial neoplasia in heterosexual and homosexual HIV-positive men with access to antiretroviral therapy. J Infect Dis. 2004;190(9):1685–91. Epub 2004/10/13. doi: 10.1086/424599 15478076.

15. Druyts E, Dybul M, Kanters S, Nachega J, Birungi J, Ford N, et al. Male sex and the risk of mortality among individuals enrolled in antiretroviral therapy programs in Africa: a systematic review and meta-analysis. Aids. 2013;27(3):417–25. Epub 2012/09/06. doi: 10.1097/QAD.0b013e328359b89b 22948271.

16. Taylor-Smith K, Tweya H, Harries A, Schoutene E, Jahn A. Gender differences in retention and survival on antiretroviral therapy of HIV-1 infected adults in Malawi. Malawi medical journal: the journal of Medical Association of Malawi. 2010;22(2):49–56. Epub 2011/05/28. doi: 10.4314/mmj.v22i2.58794 21614882

17. Chikandiwa A, Chimoyi L, Pisa PT, Chersich MF, Muller EE, Michelow P, et al. Prevalence of anogenital HPV infection, related disease and risk factors among HIV-infected men in inner-city Johannesburg, South Africa: baseline findings from a cohort study. BMC Public Health. 2017;17(Suppl 3):101–12. doi: 10.1186/s12889-017-4354-0 28832285

18. Department of Health South Africa. The South African Antiretroviral Treatment Guidelines. 2013.

19. Tamalet C, Obry-Roguet V, Ressiot E, Bregigeon S, Del Grande J, Poizot-Martin I. Distribution of human papillomavirus genotypes, assessment of HPV 16 and 18 viral load and anal related lesions in HIV positive patients: a cross-sectional analysis. J Med Virol. 2014;86(3):419–25. doi: 10.1002/jmv.23831 24154930

20. Solomon D, Davey D, Kurman R, Moriarty A, O’Connor D, Prey M, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002;287(16):2114–9. doi: 10.1001/jama.287.16.2114 11966386

21. Snijders PJ, Hogewoning CJ, Hesselink AT, Berkhof J, Voorhorst FJ, Bleeker MC, et al. Determination of viral load thresholds in cervical scrapings to rule out CIN 3 in HPV 16, 18, 31 and 33-positive women with normal cytology. Int J Cancer. 2006;119(5):1102–7. Epub 2006/03/30. doi: 10.1002/ijc.21956 16570279.

22. Xue X, Gange SJ, Zhong Y, Burk RD, Minkoff H, Massad LS, et al. Marginal and mixed-effects models in the analysis of human papillomavirus natural history data. Cancer Epidemiol Biomarkers Prev. 2010;19(1):159–69. Epub 2010/01/09. doi: 10.1158/1055-9965.EPI-09-0546 20056635

23. Bursac Z, Gauss CH, Williams DK, Hosmer DW. Purposeful selection of variables in logistic regression. Source code for biology and medicine. 2008;3:17. Epub 2008/12/18. doi: 10.1186/1751-0473-3-17 19087314

24. Wei F, Su Y, Yao X, Cui X, Bian L, Yin K, et al. Sex differences in the incidence and clearance of anal human papillomavirus infection among heterosexual men and women in Liuzhou, China: An observational cohort study. Int J Cancer. 2019;145(3):807–16. Epub 2019/03/09. doi: 10.1002/ijc.32255 30848495.

25. Patel P, Bush T, Conley L, Unger ER, Darragh TM, Henry K, et al. Prevalence, Incidence, and Clearance of Human Papillomavirus Types Covered by Current Vaccines in Men With Human Immunodeficiency Virus in the SUN Study. J Infect Dis. 2019. Epub 2019/09/20. doi: 10.1093/infdis/jiz425 31536120.

26. Hernandez AL, Efird JT, Holly EA, Berry JM, Jay N, Palefsky JM. Incidence of and risk factors for type-specific anal human papillomavirus infection among HIV-positive MSM. AIDS (London, England). 2014;28(9):1341–9. doi: 10.1097/QAD.0000000000000254 24959962.

27. Taylor S, Bunge E, Bakker M, Castellsague X. The incidence, clearance and persistence of non-cervical human papillomavirus infections: a systematic review of the literature. BMC Infect Dis. 2016;16:293. Epub 2016/06/16. doi: 10.1186/s12879-016-1633-9 27301867

28. Capra G, Nyitray AG, Lu B, Perino A, Marci R, Schillaci R, et al. Analysis of persistence of human papillomavirus infection in men evaluated by sampling multiple genital sites. Eur Rev Med Pharmacol Sci. 2015;19(21):4153–63. 26592842

29. Nyitray AG, Carvalho da Silva RJ, Baggio ML, Smith D, Abrahamsen M, Papenfuss M, et al. Six-month incidence, persistence, and factors associated with persistence of anal human papillomavirus in men: the HPV in men study. J Infect Dis. 2011;204(11):1711–22. doi: 10.1093/infdis/jir637 21964400

30. Roberts JR, Siekas LL, Kaz AM. Anal intraepithelial neoplasia: A review of diagnosis and management. World journal of gastrointestinal oncology. 2017;9(2):50–61. doi: 10.4251/wjgo.v9.i2.50 28255426

31. zur Hausen H. Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. Journal of the National Cancer Institute. 2000;92(9):690–8. Epub 2000/05/04. doi: 10.1093/jnci/92.9.690 10793105.

32. Woodman CB, Collins SI, Young LS. The natural history of cervical HPV infection: unresolved issues. Nat Rev Cancer. 2007;7(1):11–22. doi: 10.1038/nrc2050 17186016

33. Low AJ, Clayton T, Konate I, Nagot N, Ouedraogo A, Huet C, et al. Genital warts and infection with human immunodeficiency virus in high-risk women in Burkina Faso: a longitudinal study. BMC Infect Dis. 2011;11(20):1471–2334.

34. Dolev JC, Maurer T, Springer G, Glesby MJ, Minkoff H, Connell C, et al. Incidence and risk factors for verrucae in women. Aids. 2008;22. doi: 10.1097/QAD.0b013e3283021aa3 18525267

35. Ronn M, Brisson M, Looker K, Kelly H, Brock P, Mayaud P, et al., editors. Population-level impact of HPV vaccination program in high HIV prevalence settings. International Papilloma Virus 2017; Cape Town, South Africa: IPV.

36. Donovan B, Franklin N, Guy R, Grulich AE, Regan DG, Ali H, et al. Quadrivalent human papillomavirus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. Lancet Infect Dis. 2011;11(1):39–44. Epub 2010/11/12. doi: 10.1016/S1473-3099(10)70225-5 21067976.

37. Jin F, Grulich AE, Poynten IM, Hillman RJ, Templeton DJ, Law CL, et al. The performance of anal cytology as a screening test for anal HSILs in homosexual men. Cancer Cytopathol. 2016;124(6):415–24. Epub 2016/02/27. doi: 10.1002/cncy.21702 26915346.

38. Albuquerque A, Sheaff M, Stirrup O, Cappello C, Bowring J, Cuming T, et al. Performance of Anal Cytology Compared With High-Resolution Anoscopy and Histology in Women With Lower Anogenital Tract Neoplasia. Clin Infect Dis. 2018;67(8):1262–8. Epub 2018/04/17. doi: 10.1093/cid/ciy273 29659752.

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2019 Číslo 12
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