HPV Genotype Distribution in Cervical Intraepithelial Neoplasia among HIV-Infected Women in Pune, India

Arati Mane,Sten H Vermund,Arun R Risbud,Sanjay M Mehendale,Amit Nirmalkar,Vikrant V Sahasrabuddhe,Christopher B Buck

doi:10.1371/journal.pone.0038731

Abstract

BackgroundThe distribution of HPV genotypes, their association with rigorously confirmed cervical precancer endpoints, and factors associated with HPV infection have not been previously documented among HIV-infected women in India. We conducted an observational study to expand this evidence base in this population at high risk of cervical cancer.MethodsHIV-infected women (N = 278) in Pune, India underwent HPV genotyping by Linear Array assay. Cervical intraepithelial neoplasia (CIN) disease ascertainment was maximized by detailed assessment using cytology, colposcopy, and histopathology and a composite endpoint.ResultsCIN2+ was detected in 11.2% while CIN3 was present in 4.7% participants. HPV genotypes were present in 52.5% (146/278) and ‘carcinogenic’ HPV genotypes were present in 35.3% (98/278) HIV-infected women. ‘Possibly carcinogenic’ and ‘non/unknown carcinogenic’ HPV genotypes were present in 14.7% and 29.5% participants respectively. Multiple (≥2) HPV genotypes were present in half (50.7%) of women with HPV, while multiple ‘carcinogenic’ HPV genotypes were present in just over a quarter (27.8%) of women with ‘carcinogenic’ HPV. HPV16 was the commonest genotype, present in 12% overall, as well as in 47% and 50% in CIN2+ and CIN3 lesions with a single carcinogenic HPV infection, respectively. The carcinogenic HPV genotypes in declining order of prevalence overall included HPV 16, 56, 18, 39, 35, 51, 31, 59, 33, 58, 68, 45 and 52. Factors independently associated with ‘carcinogenic’ HPV type detection were reporting ≥2 lifetime sexual partners and having lower CD4+ count. HPV16 detection was associated with lower CD4+ cell counts and currently receiving combination antiretroviral therapy.ConclusionHPV16 was the most common HPV genotype, although a wide diversity and high multiplicity of HPV genotypes was observed. Type-specific attribution of carcinogenic HPV genotypes in CIN3 lesions in HIV-infected women, and etiologic significance of concurrently present non/unknown carcinogenic HPV genotypes await larger studies.

Highlights

Human immunodeficiency virus (HIV)-infected women in India and other developing countries are living longer in recent years as a result of improved access to affordable combination antiretroviral therapy drugs
HIV-infected women remain at increased risk for human papillomavirus (HPV) infection and cervical precancerous lesions progressing to invasive cervical cancer (ICC). [1,2,3]
An exploratory analysis of the risks of various single/ multiple combinations of carcinogenic and non/unknown carcinogenic types is presented in Table S1, the small numbers precluded the estimation in most models. In this cross sectional study, we have documented the diverse distribution of HPV genotypes and their associations with rigorously confirmed cervical precancerous disease endpoints, and factors associated with HPV infection among HIV-infected women in India

Summary

Introduction

Human immunodeficiency virus (HIV)-infected women in India and other developing countries are living longer in recent years as a result of improved access to affordable combination antiretroviral therapy (cART) drugs. [4,5,6] None of these studies have correlated genotype-specific HPV prevalence against rigorously verified cervical disease endpoints and immune status of HIV-infected women. The development of this evidence is critical to informing the design and delivery of HPV vaccination as well as HPV-based screening strategies for HIV-infected women. We conducted an observational study among HIV-infected women in Pune, India to expand the evidence base of HPV genotype distribution in this population. We conducted an observational study to expand this evidence base in this population at high risk of cervical cancer

Methods

Results

Conclusion