Anal cytology and p16 immunostaining for screening anal intraepithelial neoplasia in HIV-positive and HIV-negative men who have sex with men: a cross-sectional study

Abstract

Summary

Akin to cervical cancer in sexually-active women, men who have sex with men (MSM) are predisposed to anal cancers, especially those with HIV co-infection. This cross-sectional study endeavored to assess the prevalence of anal dysplasia using Pap smears and p16 immunostaining amongst Indian MSM. A total of 31 consecutive HIV-positive and 34 HIV-negative MSM, from a cohort of sexually transmitted infection clinic attendees, underwent anal cytological evaluation with Pap smear and p16 staining. Chi square test and coefficient of correlation were used for comparison. Eighteen (27.7%) had abnormal anal cytology; increased in HIV-positive as compared to HIV-negative men (35% versus 20%, p = 0.180). Similarly, both low-grade (25.8% versus 17.6%) and high-grade lesions (8.3% versus 4.8%) were comparable in HIV-positive and HIV-negative group. Thirteen (20%) smears were p16-positive with a sensitivity and specificity for anal dysplasia of 72.3% and 100%, respectively. Anal cytology may be used to screen for anal dysplasia in MSM irrespective of HIV status. Furthermore, the addition of p16, with greater specificity for high-grade lesions, may improve diagnostic accuracy especially for high-grade lesions. A larger study to further corroborate these observations is warranted.

Keywords

HIV AIDS sexually transmitted infections human papillomavirus HPV men who have sex with men MSM transgender anal intraepithelial neoplasia AIN p16 immunohistochemistry

Get full access to this article

View all access options for this article.

References

Key facts on HIV epidemic and progress in regions and countries in 2010. Based on progress report 2011: Global HIV/AIDS response, http://www.who.int/hiv/pub/progress_report2011/regional_facts/en/index1.html (2011, accessed 12 August 2012).

Palefsky

Holly

Efirdc

. Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV positive men who have sex with men. AIDS 2005; 19: 1407–1414.

WHO/ICO Information Centre on HPV and Cervical Cancer (HPV Information Centre). Human papillomavirus and related cancers in India. Summary Report 2010, http://apps.who.int/hpvcentre/statistics/dynamic/ico/country_pdf/IND.pdf (2010, accessed 21 September 2010).

Palefsky

Rubin

. The epidemiology of anal human papillomavirus and related neoplasia. Obstet Gynecol Clin North Am 2009; 36: 187–200.

Ambramowitz

Benabderrahmane

Ravaud

. Anal squamous intraepithelial lesions and condyloma in HIV-infected heterosexual men, homosexual men and women: prevalence and associated factors. AIDS 2007; 21: 1457–1465.

Ciobotaru

Leiman

St John

. Prevalence and risk factors for anal cytologic abnormalities and human papillomavirus infection in a rural population of HIV-infected males. Dis Colon Rectum 2007; 50: 1011–1016.

Palefsky

Holly

Hogeboom

. Virologic, immunologic, and clinical parameters in the incidence and progression of anal squamous intraepithelial lesions in HIV-positive and HIV-negative homosexual men. J Acquir Immune Defic Syndr Hum Retrovirol 1998; 17: 314–319.

Chin-Hong

Vittinghoff

Cranston

. Age-related prevalence of anal cancer precursors in homosexual men: the EXPLORE study. J Natl Cancer Inst 2005; 97: 896–905.

Sonnex

Scholefield

Kocjan

. Anal human papillomavirus infection: a comparative study of cytology, colposcopy and DNA hybridisation as methods of detection. Genitourin Med 1991; 67: 21–25.

10.

Walts

Bose

. p16, Ki-67, and BD ProEx™C immunostaining: a practical approach for diagnosis of cervical intraepithelial neoplasia. Hum Pathol 2009; 40: 957–964.

11.

Walts

Lechago

Bose

. P16 and Ki67 immunostaining is a useful adjunct in the assessment of biopsies for HPV-associated anal intraepithelial neoplasia. Am J Surg Pathol 2006; 30: 795–801.

12.

Samama

Lipsker

Boehm

. P16 expression in relation to human papillomavirus in anogenital lesions. Hum Pathol 2006; 37: 513–519.

13.

Bernard

Butler

Sandweiss

. Anal intraepithelial neoplasia: correlation of grade with p16 immunohistochemistry and HPV in situ hybridization. Appl Immunohistochem Mol Morphol 2008; 16: 215–220.

14.

Darvishian

Stier

Soslow

. Immunoreactivity of p16 in anal cytology specimens: histologic correlation. Cancer 2006; 108: 66–71.

15.

Tramujas da Costa E Silva

Coelho Ribeiro

Santos Gimenez

. Performance of p16INK4a immunocytochemistry as a marker of anal squamous intraepithelial lesions. Cancer Cytopathol 2011; 119: 167–176.

16.

Phanuphak

Sahasrabuddhe

. Anal squamous intraepithelial lesions among HIV positive and HIV negative men who have sex with men in Thailand. Sex Transm Infect 2009; 85: 503–507.

17.

Yang

Zhang

. Association of human papillomavirus infection and abnormal anal cytology among HIV-infected MSM in Beijing, China. PLoS One 2012; 7: e35983–e35983.

18.

Sayers

McMillian

Mcgoogan

. Anal cytological abnormalities in HIV-infected homosexual men. Int J STD AIDS 1998; 9: 37–40.

19.

Solomon

Davey

Kurman

. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 2002; 287: 2114–2119.

20.

Rabkin

Yellin

. Cancer incidence in a population with a high prevalence of infection with human immunodeficiency virus type 1. J Natl Cancer Inst 1994; 86: 1711–1716.

21.

Goedert

Coté

Virgo

. Spectrum of AIDS-associated malignant disorders. Lancet 1998; 351: 1833–1839.

22.

Palefsky

Holly

Hogeboom

. Anal cytology as a screening tool for anal squamous intraepithelial lesions. J Acquir Immune Defic Syndr Hum Retrovirol 1997; 14: 415–422.

23.

Setia

Lindan

Jerajani

. Men who have sex with men and transgenders in Mumbai, India: an emerging risk group for STIs and HIV. Ind J Dermatol Venereol Leprol 2006; 72: 425–431.

24.

Piketty

Darragh

Da Costa

. High prevalence of anal human papillomavirus infection and anal cancer precursors among HIV-infected persons in the absence of anal intercourse. Ann Intern Med 2003; 138: 453–459.

25.

Repiso Jiménez

Frieyro-Elicegui

Padilla-España

. Anal intraepithelial neoplasia in sexually transmitted diseases outpatient clinic: correlation with cytological screening. J Eur Acad Dermatol Venereol 2013. Mar 5. [Epub ahead of print].

26.

Bean

Meara

Vollmer

. p16 improves the interobserver agreement in diagnosis of anal intraepithelial neoplasia. J Low Gen Trac Dis 2009; 13: 145–153.

27.

Kostopoulou

Samara

Kollia

. Different patterns of P16 immunoreactivity in cervical biopsies: correlation to lesion grade and HPV detection, with a review of literature. Eur J Gynaecol Oncol 2011; 32: 54–61.

28.

Kalof

Cooper

. p16/ink4a Immunoexpression: surrogate marker of high-risk HPV and high-grade cervical intraepithelial neoplasia. Adv Anat Pathol 2006; 13: 190–194.

29.

Srikrishnan

Sivaram

. High HIV prevalence and risk behaviors in men who have sex with men in Chennai, India. J Acquir Immune Defic Syndr 2004; 35: 314–319.

30.

Hernandez

Lindan

Mathur

. Sexual behaviour among men who have sex with women, men, and hijras in Mumbai, India—multiple sexual risks. AIDS Behav 2006; 10: 5–16.