Anal Cancer Risk Remains High among HIV Positive Men and Women on HAART: SUN Study

People with HIV/AIDS are at higher risk for precancerous cell changes due to "high risk" types of human papillomavirus (HPV) infection. While invasive cervical cancer is uncommon in developed countries due to routine Pap smears, such screening is not yet recommended for anal cancer (though many experts believe it should be).

The elevated risk of precancerous changes - known variously as dysplasia, intraepithelial neoplasia, and squamous intraepithelial lesions (SIL) -- in HIV positive people appears linked to immune suppression. However, several studies have shown that rates of anogenital cancer have not fallen, and in fact have risen, since the advent of HAART -- likely because effective anti-HIV therapy keeps patients alive long enough to develop progressive malignancies.

At the 15th Conference on Retroviruses and Opportunistic Infections (CROI 2008) last month in Boston, researchers looked at rates of and risk factors for anal cancer in the SUN Study, an ongoing prospective natural history study of HIV positive outpatients seen at clinics in Denver, Minneapolis, Providence, and St. Louis.

At baseline, and annually thereafter, all patients complete a behavioral risk questionnaire and provided anorectal specimen for cytological examination and HPV detection and genotyping. Complete data at both baseline and 1-year follow-up visits were available for 371 participants.

Results

• At baseline, 100 patients were diagnosed with low-grade anal SIL and 28 with high-grade SIL; these patients were excluded from the current analysis.

• Of the remaining 243 patients with negative anal cytology or atypical squamous cells, 76% were male and 86% had detectable HPV.

• At 1 year of follow-up, the median age was 42 years, 94% were receiving HAART, 57% had a CD4 cells count of at least 500 cells/mm3 (median 530 cells/mm3), and 79% had undetectable HIV viral load.

• Anal cytology results at 1 year were:

• Negative for any abnormal changes in 190 patients (78%);

• Atypical squamous cells in 23 patients (9%);

• Low-grade SIL in 25 (10%);

• High-grade SIL in 5 (2%).

• A univariate analysis showed that the following factors were significantly associated with incident (new onset) SIL (all P < 0.05):

• At least 1 high-risk HPV type detected at each visit;

• Detectable HIV viral load at each visit;

• Current cigarette smoking;

• Non-adherence to HAART (defined as missing at least 1 dose in a 3-day period);

• Use of 1 or more illicit drugs (other than marijuana) during the past 30 days.

• In a multivariate analysis, detection of a high-risk HPV type at each visit (OR 10.4; P = 0.026), detectable HIV viral load at each visit (OR 3.8; P = 0.015) and illicit drug use (OR 6.4; P = 0.047) remained associated with abnormal anal cytology.

Conclusion

"In this large cohort of generally healthy, HIV-infected men and women, the incidence of anal SIL at 1 year was 12%," the researchers concluded.

Notably, they added, "CD4 level and high-risk sexual behaviors (e.g., unprotected anal sex, multiple partners) in the previous year were not associated with incident SIL" - a finding that conflicts with some prior research.

The investigators recommended that, "Clinicians may wish to consider anal cytology and HPV screening in HIV-infected patients, particularly if they are found repeatedly to have detectable HIV viral loads."

CDC, Atlanta, GA; Univ of California, San Francisco, CA; Miriam Hosp, Providence, RI; Park-Nicollet Inst, Minneapolis, MN; Washington Univ School of Med, St Louis, MO.

3/21/08

Reference

L Conley, T Bush, T Darragh, and others. Incidence and Predictors of Anal Squamous Intraepithelial Lesions in the SUN Study after 1 Year of Follow-up. 15th Conference on Retroviruses and Opportunistic Infections (CROI 2008). Boston, MA. February 3-6, 2008. Abstract 1022.