www.hivandhepatitis.com

ICAAC 2011: HPV Testing and Pap Smears Identify Anal Cancer Risk in HIV+ Men

Human papillomavirus (HPV) testing and anal Pap testing can detect abnormal cell changes that could progress to anal cancer in HIV positive gay men at an earlier and more treatable stage, and is likely to be cost-effective, according to a study presented at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2011) this month in Chicago. 

Anal cancer, caused by certain high-risk or oncogenic (cancer-causing) types of HPV, remains prevalent among HIV positive men who have sex with men (MSM) in the era of effective antiretroviral therapy (ART). Yet regular HPV testing and Pap smears (in which a sample of cells is examined under a microscope) are not widely considered part of the standard of care for this population.

Some clinicians and advocates believe that these tests should be routine. Regular cervical Pap smears are recommended for all women, and have dramatically reduced the rate of death due to cervical cancer since they were widely adopted in the 1950s.

Invasive cervical cancer -- caused by the same high-risk HPV types as anal cancer -- is considered an AIDS-defining opportunistic illness. Anal cancer is not so classified, though many experts and advocates think it should be, since rates are much higher among HIV positive compared with HIV negative men MSM.

Investigators at University Hospital -- Virgen de las Nieves in Granada, Spain, prospectively analyzed the prevalence of high-risk HPV genotypes and anal dysplasia (abnormal cell changes that can progress to cancer) among gay/bisexual men.

They sought to determine the sensitivity, specificity, positive (PPV), and negative predictive value (NPV) of HPV testing and Pap smears, as well as their cost-effectiveness. Sensitivity is how well a test accurately identifies a person with a condition, while specificity is how well it accurately rules out those who do not have the condition.

The study included 114 HIV positive MSM seen during 2008-2010. The average age was 31 years. The group had well-controlled HIV disease overall; about 60% were on ART and their nadir (lowest-ever) CD4 cell count was above 450 cells/mm³, indicating that they had never had severe immune deficiency. About half were smokers (a known risk factor for anal cancer) and most (71%) reported using condoms for anal sex.

At each study visit the researchers collected 2 swab specimens from the anal canal, using 1 to perform a HPV PCR test and the other for Pap cytology examination. Testing was repeated every 6 months if tests showed oncogenic HPV types or abnormal cells, or once annually if tests were normal. Men who had oncogenic HPV and/or low-grade intraepithelial neoplasia (mild-to-moderate cell abnormalities) on 2 occasions, or high-grade neoplasia (severe or pre-cancerous abnormalities) on 1 occasion. underwent anoscopy (rectoscopy), in which the anus is examined and a tissue sample taken for biopsy using a lighted magnifying instrument.

Results

• 91% of patients were found to have anal HPV infection.
• The most common HPV types were 6 (13%), 11 (13%),16 (26%),18 (15%), 51 (15%) and CP6 108 (15%) (HPV 16 and 18 are oncogenic, 6 and 11 cause genital warts).
• 71% of the Pap smears showed dysplasia, or abnormal cell growth.
• One-quarter of participants underwent 26 anoscopic examinations and biopsies, revealing:
  • 9 men (35%) with mild anal intraepithelial neoplasia (AIN I);
  • 4 men (15%) with moderate neoplasia (AIN II);
  • 1 man (4%) with severe neoplasia (AIN III);
  • 3 men (12%) with anal carcinoma in situ (cancer without metastasis).
• HPV testing and Pap smears had the following accuracy:
  • Sensitivity: 22% for HPV tests, 88% for Pap smears;
  • Specificity: 80% and 50%, respectively;
  • Positive predictive value: 80% and 82%, respectively;
  • Negative predictive value: 21% and 60%, respectively;
• The cost of the testing protocol was Euro 320-400 (about $430-$550) per person per year.

"Our protocol for diagnosis and follow-up to dysplasia of the anal mucosa in [HIV positive MSM] is cost effective for several reasons," the researchers concluded. "One of them is the high prevalence of dysplasic lesions and colonization by oncogenic HPV; another because in those patients in whom there is a high suspicion of malignant lesions, [this] is confirmed by biopsy in up to 66.6% of the cases."

Investigator affiliation: University Hospital -- Virgen de las Nieves, Granada, Spain.

9/30/11

Reference

C Hidalgo Tenorio, M Rivero, F Jarilla F, et al. Utility and performance of a diagnostic protocol and follow-up to the dysplasia of the anal mucosa of HIV-positive patients men who have sex with men (MSM). 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2011). Chicago, September 17-20, 2011. Abstract H1-1397.