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ICAAC 2014: Anal HPV Infection and Dysplasia Common in HIV+ Women and Gay Men

Anal infection with high-risk human papillomavirus (HPV) types was common among women with HIV in France, while a Spanish study found a low rate of pre-cancerous anal cell changes in HIV positive women compared with men who have sex with men, researchers reported at the recent 54th Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington, DC.

HPV triggers abnormal cell growth and certain high-risk types can cause cancer of the cervix, anal canal, and genitals. Although findings have been inconsistent, several studies have reported associations between HIV infection, CD4 T-cell count, and higher rates of HPV infection, being infected with multiple types of HPV, lower likelihood of spontaneous HPV clearance, and faster progression to abnormal cell changes (dysplasia) or more serious pre-cancerous abnormalities (neoplasia).

Cervical cancer -- an AIDS-defining malignancy -- is uncommon in wealthy countries thanks to routine cervical examination using Pap smears and/or HPV testing, but anal screening is much less widely done.

French Study

Investigators with the ANRS-C017 VIHGY Study Group prospectively evaluated the prevalence of anal and cervical infection with different HPV types in 311 HIV positive women from clinical sites across France. While the main study focused on cervical infection, an anal substudy was performed in 2012.

The median age was 45 years and 43% of the women came from sub-Saharan Africa. Almost all were on antiretroviral therapy (ART) and 84% had undetectable HIV viral load. The median current CD4 count was approximately 600 cells/mm³, but the median nadir (lowest-ever) level was about 200 cells/mm³. Half the women reported a history of low-grade cervical lesions (LSIL), and 25% had undergone treatment including conization (removal of a cone-shaped section of the cervix). All participants had cervical and anal samples taken less than 6 months apart and the median follow-up period was about 16 years.

Results

• 33% of the women had high-risk HPV in the cervix and 55% had high-risk HPV in the anal canal.
• In the anal canal, HPV-16 -- the most frequent cause of cancer -- was the most common type, at 13%, and 81% were infected with multiple HPV types.
• In the cervix, HPV-16 was the second most common type, at 5%, and 66% had multiple types.
• Most high-risk HPV types -- with the exception of HPV-35 -- were found more often in anal compared with cervical samples.
• There was poor concordance, or matches, between high-risk HPV types found in the cervix and anal canal of individual women.
• 23% women had high-risk HPV in both the cervix and anal canal, 31% had anal but not cervical high-risk HPV, 10% had cervical but not anal high-risk HPV, and 35% were negative for high-risk HPV at both sites.
• In a multivariate analysis, factors associated with high-risk anal HPV included a history of cervical lesions, infection with HPV types other than HPV-16, a current CD4 count below 350 cells/mm³, and being in the 40-49 year age range.
• Factors associated with high-risk cervical HPV included a history of cervical lesions, anal infection with HPV-16 or other types, nadir (but not current) CD4 count below 350 cells/mm³, and being from sub-Saharan Africa

"The higher prevalence of high risk-HPV types in anal samples gives cause for concern," the researchers cautioned. "We hypothesize that the longer persistence of non-transforming infection in the cervix allows high risk-HPV transmission to the anal canal."

"In the absence of screening, persistent infection open[s] the door for future anal disease and cancer in HIV positive women," they continued. "Anal cancer screening could be offered to HIV-infected women during their gynecological examination."

Spanish Study

In a related study, Carmen Hidalgo Tenorio from University Hospital Virgen de las Nieves and colleagues looked at the prevalence of and risk factors for anal lesions in HIV positive women and men who have sex with men in southern Spain. They also analyzed the role of anal cytology (cell examination) and high-risk HPV PCR testing in diagnosis of anal intraepithelial neoplasia.

This analysis included 77 women and 183 gay/bisexual men with HIV. The average age was 43 years for the women and 37 for the men. The median CD4 count was high -- above 650 cells/mm³ -- for both groups. However, unlike the prior study, most were not yet on ART. About 30% of the women and all the men reported anal sex and two-thirds of the women and half the men smoked -- both risk factors for anal cancer.

The researchers collected anal mucosa samples for cytology and HPV genotyping; cervical samples were also collected from the women. People with evidence of anal lesions (SIL) or anal high-risk HPV infection also received anoscopy, or examination with a magnifying instrument.

Results

• Women:

o   18% of the women had a history of cervical dysplasia and 10% had a current diagnosis of cervical dysplasia.

o   31% of the women had anal SIL, including 1% with high-grade SIL.

o   50% had high-risk HPV, with the most common type being HPV-16 (16%).

o   27 women underwent anoscopies, which revealed that 56% had mild neoplasia (AIN-1) and 19% had moderate or advanced neoplasia (AIN-2/3).

o   If anal cytology was normal, only 27% of anoscopies were normal, 55% showed low-grade SIL, and 18% showed high-grade SIL (equivalent to AIN-2/3).

o   If PCR testing was positive for high-risk HPV, only 20% had normal tissue histology, 55% had low-grade SIL, and 25% had high-grade SIL.

o   Risk factors for anal SIL included anal-genital condylomas (warts) and presence of HPV-16.

• Men:

o   51% of the men had anal SIL, including 4% with high-grade SIL.

o   75% had high-risk HPV, again most often HPV-16 (31%).

o   183 men had anoscopies, revealing that 48% had AIN-1 and 19% had AIN-2/3.

The prevalence of high-grade SIL in women with HIV is low compared with HIV positive men who have sex with men, the researchers concluded. "Introducing PCR HPV genotype evaluation improves screening success of AIN over that of cytology alone," they advised.

10/3/14

References

I Heard, I Poizot-Martin, V Potard, et al (ANRS-C017 VIHGY Study Group). High Prevalence of Oncogenic HPV Infection in Anal Canal versus Cervix in HIV Infected Women in France. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2014). Washington, DC, September 5-9, 2014.Abstract H-1199.

C Hidalgo Tenorio, C Gil Anguita, J Ramirez Taboada, et al. Prevalence and Risk Factors for Anal Squamous Intraepithelial Lesions (ASIL) in Women Living with HIV (WLHIV), in the Era of Effective Therapy. 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2014). Washington, DC, September 5-9, 2014.Abstract H-1641.