HPV genotype distribution in cervical intraepithelial neoplasia among HIV-infected women in Pune, India

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

Abstract

Background: The 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.

Methods: HIV-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.

Results: CIN2+ 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.

Conclusion: HPV16 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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Bar graphs showing HPV genotype…
Figure 1. Bar graphs showing HPV genotype prevalence by age categories among HIV-infected women in Pune, India.
HPV prevalence levels (as percentages) are displayed on the Y-axis, with various carcinogenicity groupings (any HPV type, carcinogenic HPV type, possibly carcinogenic HPV types, and non/unknown carcinogenic types) shown as individual bar graphs grouped by age categories (≤25, 26–30, 31–35, 36–40, & ≥41 years) on X-axis.
Figure 2. Bar graphs showing HPV genotype…
Figure 2. Bar graphs showing HPV genotype prevalence by CD4+ cell count categories among HIV-infected women in Pune, India.
HPV prevalence levels (as percentages) are displayed on the Y-axis, with various carcinogenicity groupings (any HPV type, carcinogenic HPV type, possibly carcinogenic HPV types, and non/unknown carcinogenic types) shown as individual bar graphs grouped by CD4+ count categories (≤199, 200–299, 300–399, 400–499, ≥500 /µL) on X-axis.

References

    1. Sahasrabuddhe VV, Bhosale RA, Joshi SN, Kavatkar AN, Nagwanshi CA, et al. Prevalence and predictors of colposcopic-histopathologically confirmed cervical intraepithelial neoplasia in HIV-infected women in India. PLoS One. 2010;5:e8634.
    1. Strickler HD, Burk RD, Fazzari M, Anastos K, Minkoff H, et al. Natural history and possible reactivation of human papillomavirus in human immunodeficiency virus-positive women. J Natl Cancer Inst. 2005;97:577–586.
    1. Palefsky JM, Holly EA. Chapter 6: Immunosuppression and co-infection with HIV. J Natl Cancer Inst Monogr. 2003. pp. 41–46.
    1. Peedicayil A, Thiyagarajan K, Gnanamony M, Pulimood SA, Jeyaseelan V, et al. Prevalence and risk factors for human papillomavirus and cervical intraepithelial neoplasia among HIV-positive women at a tertiary level hospital in India. J Low Genit Tract Dis. 2009;13:159–164.
    1. Sarkar K, Pal R, Bal B, Saha B, Bhattacharya S, et al. Oncogenic HPV among HIV infected female population in West Bengal, India. BMC Infect Dis. 2011;11:72.
    1. Joshi SN, Gopalkrishna V, Kumar BK, Dutta S, Nyaynirgune P, et al. Cervical squamous intra-epithelial changes and human papillomavirus infection in women infected with human immunodeficiency virus in Pune, India. J Med Virol. 2005;76:470–475.
    1. Solomon D, Davey D, Kurman R, Moriarty A, O'Connor D, et al. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002;287:2114–2119.
    1. Richart RM. A modified terminology for cervical intraepithelial neoplasia. Obstet Gynecol. 1990;75:131–133.
    1. Coutlee F, Gravitt P, Kornegay J, Hankins C, Richardson H, et al. Use of PGMY primers in L1 consensus PCR improves detection of human papillomavirus DNA in genital samples. J Clin Microbiol. 2002;40:902–907.
    1. Coutlee F, Rouleau D, Petignat P, Ghattas G, Kornegay JR, et al. Enhanced detection and typing of human papillomavirus (HPV) DNA in anogenital samples with PGMY primers and the Linear array HPV genotyping test. J Clin Microbiol. 2006;44:1998–2006.
    1. Kornegay JR, Roger M, Davies PO, Shepard AP, Guerrero NA, et al. International proficiency study of a consensus L1 PCR assay for the detection and typing of human papillomavirus DNA: evaluation of accuracy and intralaboratory and interlaboratory agreement. J Clin Microbiol. 2003;41:1080–1086.
    1. Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, et al. A review of human carcinogens–Part B: biological agents. Lancet Oncol. 2009;10:321–322.
    1. Clifford GM, Goncalves MA, Franceschi S. Human papillomavirus types among women infected with HIV: a meta-analysis. AIDS. 2006;20:2337–2344.
    1. Sahasrabuddhe VV, Mwanahamuntu MH, Vermund SH, Huh WK, Lyon MD, et al. Prevalence and distribution of HPV genotypes among HIV-infected women in Zambia. Br J Cancer. 2007;96:1480–1483.
    1. Singh DK, Anastos K, Hoover DR, Burk RD, Shi Q, et al. Human papillomavirus infection and cervical cytology in HIV-infected and HIV-uninfected Rwandan women. J Infect Dis. 2009;199:1851–1861.
    1. Moodley JR, Constant D, Hoffman M, Salimo A, Allan B, et al. Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa: a cross-sectional study. BMC Cancer. 2009;9:275.
    1. Didelot-Rousseau MN, Nagot N, Costes-Martineau V, Valles X, Ouedraogo A, et al. Human papillomavirus genotype distribution and cervical squamous intraepithelial lesions among high-risk women with and without HIV-1 infection in Burkina Faso. Br J Cancer. 2006;95:355–362.
    1. Bollen LJ, Chuachoowong R, Kilmarx PH, Mock PA, Culnane M, et al. Human papillomavirus (HPV) detection among human immunodeficiency virus-infected pregnant Thai women: implications for future HPV immunization. Sex Transm Dis. 2006;33:259–264.
    1. Hernandez BY, Vu Nguyen T. Cervical human papillomavirus infection among female sex workers in southern Vietnam. Infect Agent Cancer. 2008;3:7.
    1. Melgaco FG, Rosa ML, Augusto EF, Haimuri JG, Jacintho C, et al. Human papillomavirus genotypes distribution in cervical samples from women living with human immunodeficiency virus. Arch Gynecol Obstet. 2011;283:809–817.
    1. Coelho Lima BM, Golub JE, Tonani Mattos A, Freitas LB, Cruz Spano L, et al. Human papillomavirus in women with and without HIV-1 infection attending an STI clinic in Vitoria, Brazil. J Int Assoc Physicians AIDS Care (Chic) 2009;8:286–290.
    1. Tornesello ML, Duraturo ML, Giorgi-Rossi P, Sansone M, Piccoli R, et al. Human papillomavirus (HPV) genotypes and HPV16 variants in human immunodeficiency virus-positive Italian women. J Gen Virol. 2008;89:1380–1389.
    1. Kitchener H, Nelson L, Adams J, Mesher D, Sasieni P, et al. Colposcopy is not necessary to assess the risk to the cervix in HIV-positive women: an international cohort study of cervical pathology in HIV-1 positive women. Int J Cancer. 2007;121:2484–2491.
    1. Hankins C, Coutlee F, Lapointe N, Simard P, Tran T, et al. Prevalence of risk factors associated with human papillomavirus infection in women living with HIV. Canadian Women's HIV Study Group. CMAJ. 1999;160:185–191.
    1. Luque AE, Jabeen M, Messing S, Lane CA, Demeter LM, et al. Prevalence of human papillomavirus genotypes and related abnormalities of cervical cytological results among HIV-1-infected women in Rochester, New York. J Infect Dis. 2006;194:428–434.
    1. Strickler HD, Palefsky JM, Burk RD. HPV types present in invasive cervical cancers of HIV-seropositive women. Int J Cancer. 2008;123:1224–1225.
    1. Strickler HD, Palefsky JM, Shah KV, Anastos K, Klein RS, et al. Human papillomavirus type 16 and immune status in human immunodeficiency virus-seropositive women. J Natl Cancer Inst. 2003;95:1062–1071.
    1. McKenzie ND, Kobetz EN, Hnatyszyn J, Twiggs LB, Lucci JA 3rd. Women with HIV are more commonly infected with non-16 and −18 high-risk HPV types. Gynecol Oncol. 2010;116:572–577.
    1. Broker TR, Jin G, Croom-Rivers A, Bragg SM, Richardson M, et al. Viral latency–the papillomavirus model. Dev Biol (Basel) 106: 443–451; discussion 452–443, 465–475. 2001.
    1. Palefsky JM, Minkoff H, Kalish LA, Levine A, Sacks HS, et al. Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women. J Natl Cancer Inst. 1999;91:226–236.
    1. Nicol AF, Nuovo GJ, Salomao-Estevez A, Grinsztejn B, Tristao A, et al. Immune factors involved in the cervical immune response in the HIV/HPV co-infection. J Clin Pathol. 2008;61:84–88.
    1. Stanley M. Prospects for new human papillomavirus vaccines. Curr Opin Infect Dis. 2010;23:70–75.
    1. Levi JE, Kleter B, Quint WG, Fink MC, Canto CL, et al. High prevalence of human papillomavirus (HPV) infections and high frequency of multiple HPV genotypes in human immunodeficiency virus-infected women in Brazil. J Clin Microbiol. 2002;40:3341–3345.
    1. Luque AE, Hitti J, Mwachari C, Lane C, Messing S, et al. Prevalence of human papillomavirus genotypes in HIV-1-infected women in Seattle, USA and Nairobi, Kenya: results from the Women's HIV Interdisciplinary Network (WHIN). Int J Infect Dis. 2010;14:e810–814.
    1. Hawes SE, Critchlow CW, Sow PS, Toure P, N'Doye I, et al. Incident high-grade squamous intraepithelial lesions in Senegalese women with and without human immunodeficiency virus type 1 (HIV-1) and HIV-2. J Natl Cancer Inst. 2006;98:100–109.
    1. Moscicki AB, Ellenberg JH, Farhat S, Xu J. Persistence of human papillomavirus infection in HIV-infected and -uninfected adolescent girls: risk factors and differences, by phylogenetic type. J Infect Dis. 2004;190:37–45.
    1. Nuovo GJ, Darfler MM, Impraim CC, Bromley SE. Occurrence of multiple types of human papillomavirus in genital tract lesions. Analysis by in situ hybridization and the polymerase chain reaction. Am J Pathol. 1991;138:53–58.
    1. Vaccarella S, Franceschi S, Snijders PJ, Herrero R, Meijer CJ, et al. Concurrent infection with multiple human papillomavirus types: pooled analysis of the IARC HPV Prevalence Surveys. Cancer Epidemiol Biomarkers Prev. 2010;19:503–510.
    1. Wentzensen N, Schiffman M, Dunn T, Zuna RE, Gold MA, et al. Multiple human papillomavirus genotype infections in cervical cancer progression in the study to understand cervical cancer early endpoints and determinants. Int J Cancer. 2009;125:2151–2158.
    1. Steinau M, Swan DC, Unger ER. Type-specific reproducibility of the Roche linear array HPV genotyping test. J Clin Virol. 2008;42:412–414.
    1. Joint United Nations Programme on HIV/AIDS. Global report: UNAIDS report on the global AIDS epidemic. Geneva, Switzerland: Joint United Nations Programme on HIV/AIDS. pp. v. 2010.
    1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–2917.
    1. Sahasrabuddhe VV, Luhn P, Wentzensen N. Human papillomavirus and cervical cancer: biomarkers for improved prevention efforts. Future Microbiol. 2011;6:1083–1098.

Source: PubMed

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