ICAAC 2012: Progression of Anal Neoplasia is Common among Gay Men with HIV

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Nearly 40% of HIV positive men with low-grade anal neoplasia may progress to high-grade neoplasia or anal cancer, according to a Spanish study presented at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) this week in San Francisco. Younger age and shorter duration of HIV infection were risk factors for worsening disease.

Anal cancer caused by human papillomavirus (HPV) is more common among HIV positive men who have sex with men (MSM) compared with the general population. While AIDS-defining cancers have declined since the advent of effective combination antiretroviral therapy (ART), some studies indicate that anal cancer has become more common as people with HIV live longer.

HPV triggers abnormal cell growth including warts and neoplasia. Certain high-risk or oncogenic types -- in particular HPV-16 and HPV-18 -- are the usual cause of anal and cervical cancer. But oncogenic HPV infection does not always result in tissue abnormalities, mild or low-grade dysplasia (abnormal tissue) does not always progress to more severe or high-grade neoplasia, and high-grade neoplasia does not always lead to cancer.

Carmen Hidalgo, MD, from Hospital Universitario Virgen de las Nieves in Granada, Spain, and colleagues looked at predictors of progression from low-grade anal intraepithelial neoplasia (AIN) to high-grade AIN or anal carcinoma in situ (localized cancer). They also evaluated the role of different screening methods for detecting high-grade AIN or anal cancer.

This prospective cohort study included 163 HIV positive MSM seen at the hospital between April 2010 and April 2012 who participated in an anal neoplasia screening program.

The participants' average age was 36 years and they had been diagnosed with HIV for a median of 54 months. They reported a median of 1 sexual partner during the past year and nearly 75% said they used condoms. Only 3% were coinfected with hepatitis B or C. Half were smokers.

Participants had well-preserved immune function, with a current median CD4 T-cell count of about 600 cells/mm3 and a nadir (lowest-ever) count of 375 cells/mm3. Three-quarters were on antiretroviral therapy and 85% had undetectable HIV viral load.

The men underwent baseline and follow-up evaluations that included anal cytology tests (examination of a cell sample under a microscope, better known as a Pap smear), PCR tests for HPV, and anoscopy (visual examination using a lighted magnifying instrument, with application of vinegar to make lesions turn white).

Results

o   71% had modest cell abnormalities (referred to as low-grade squamous intraepithelial lesions, or LSIL);

o   3% had serious abnormalities (high-grade squamous intraepithelial lesions, or HSIL);

o   27% had atypical squamous cells of undetermined significance (ASCUS).

o   28% were normal;

o   47% had low-grade AIN (also referred to as grade 1);

o   17% had high-grade AIN (also called grade 2/3);

o   8% had anal cancer in situ.

o   Progressors had an average age of 29.5 years compared with 34.1 years for non-progressors;

o   Intervals since HIV diagnosis were 44 and 60 months, respectively.

The finding that only age and time since HIV diagnosis significantly predicted neoplasia progression conflicts with previous studies that have seen a link between anal neoplasia prevalence or progression and several of these factors, especially HPV type and degree of immune deficiency. However, only 21 people with low-grade AIN completed follow-up in this analysis, and small samples sizes make it more difficult to demonstrate statistical significance.

The researchers concluded that anal cytology and high-risk HPV testing together have good sensitivity and negative predictive value, adding that if both tests are normal, a patient can be presumed not have neoplasia, allowing them to avoid unnecessary anoscopy.

Offering a different opinion at an ICAAC "meet-the-experts" session earlier in the week, Joel Palefsky, MD, from the University of California at San Francisco recommended that all HIV positive MSM over age 30 should be screened for anal neoplasia using both cytology testing and digital-rectal examination.

Some abnormalities that do not show up on a Pap smear may be felt by a manual exam and vice-versa, he explained. HPV testing may be less useful because its prevalence in this population is "almost 100%."

Palefsky added that, in his opinion, an individual with any degree of abnormality should be followed-up with anoscopy, not just those with suspected high-grade neoplasia. He acknowledged, however, that cost and limited "people power" may make this difficult to put into practice.

9/13/12

References

C Hidalgo Tenorio, M Rivero, C Gil Anguita, et al. Risk Factors in the Progression of Low Grade Intraepithelial Neoplasia (LGAIN) to High Grade Intraepithelial Neoplasia (HGAIN) in a Cohort of HIV-MSM. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco. September 9-12, 2012. Abstract H-1921.

J Palefsky and E Kojic. Prevention of Anal Cancer in HIV-Infection: From Early Detection to Vaccination. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco. September 9-12, 2012. Meet-the-experts session.