Anal cancer increases in French HIV cohort, despite use of antiretroviral therapy

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The incidence of anal cancer has increased dramatically in France despite the introduction of potent HIV therapy, researchers reported at the Sixteenth International AIDS Conference on Tuesday August 15th.

Anal cancer is caused by certain types of human papillomavirus (HPV). Research has shown that people with HIV are more likely to be infected with HPV, and appear more likely to develop pre-cancerous cell changes known as squamous intraepithelial lesions (SIL) and to progress to cancer. Several recent studies suggest that rates of anal HPV infection and SIL have not declined in the era of effective HIV therapy.

Christophe Piketty and colleagues conducted a study to determine the incidence rate and risk factors for anal cancer in HIV-positive individuals. They collected data on cases of anal cancer recorded in the French Database on HIV, which included 81,752 HIV-positive patients, between 1992 and 2003. Anal cancer incidence rates were calculated for three time periods:

Glossary

human papilloma virus (HPV)

Some strains of this virus cause warts, including genital and anal warts. Other strains are responsible for cervical cancer, anal cancer and some cancers of the penis, vagina, vulva, urethra, tongue and tonsils.

squamous intraepithelial lesion (SIL)

This term is used to describe the detection of abnormal cells that have been ‘transformed’ by HPV into a possibly pre-cancerous state. According to the degree of cell change this will be called low-grade or high-grade SIL (LSIL or HSIL). If SIL is detected, a colposcopy will usually be ordered.

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

metastasis

The process by which cancer cells break away from where they first formed (primary tumour), travel through the blood or lymph system, and form new tumours in other parts of the body. The metastatic tumour is the same type of cancer as the primary tumour. 

lesions

Small scrapes, sores or tears in tissue. Lesions in the vagina or rectum can be cellular entry points for HIV.

  • Pre-potent HIV therapy: January 1992 through March 1996;
  • Early potent HIV therapy: April 1996 through 1998;
  • Recent potent HIV therapy: January 1999 through December 2003.

A total of 207 patients were diagnosed with anal cancer, of whom 97 had confirmed new cases during the study period. Of the 97 cases, nine (9%) were in women, 23 (23%) were in men who reported no sexual contact with men, and 65 (67%) were in men who have sex with men. Of all the anal cancer cases, 67% were in gay or bisexual men.

Among the patients diagnosed with anal cancer, the median age was 42 years. The median CD4 cell count at the time of diagnosis was 265 cells/mm3, and the median nadir (lowest ever) CD4 count was 80 cells/mm3. About 42% had an AIDS-defining condition and 74% were receiving potent HIV therapy prior to anal cancer diagnosis, with a median duration of about five years.

By time period, 10 cases were diagnosed in the pre-potent HIV therapy period, 13 in the early potent HIV therapy period, and 74 in the recent potent HIV therapy period. The overall anal cancer incidence rates were 10 per 100,000 person years (PY) during the pre-HIV therapy era, compared with 13 per 100,000 PY during the early potent HIV therapy period and 37 per 100,000 PY during the recent potent HIV therapy period. Relative to the pre-potent HIV therapy period, the incidence of anal cancer was about four times higher during the recent potent HIV therapy period.

Between the pre-potent HIV therapy and the recent potent HIV therapy periods, anal cancer incidence rates rose among women, heterosexual men, and men who have sex with men. Looking only at the latter group, the incidence rate rose from about 16 cases per 100,000 PY during the pre-potent HIV therapy period to about 27 per 100,000 PY during the early potent HIV therapy period to about 62 per 100,000 PY during the recent HAART period.

In a multivariate analysis controlling for potentially confounding factors, anal cancer risk was independently associated with gender and sexual risk category (p

Among the patients with anal cancer, 21 developed metastases (spreading to other areas), 55 did not, and follow-up data were unavailable for 21. About one-third received radiation therapy or chemotherapy, 12 underwent only surgery, and about half received both forms of treatment. There were a total of 37 deaths, 24 of them due to anal cancer. The probability of surviving three years after anal cancer diagnosis was about 75%.

The researchers concluded that there has been “a significant increase in the incidence of anal cancer since the introduction of [potent HIV therapy] into standard care for patients in France.” They added that their results agree with those from other studies showing that “[potent HIV therapy] exhibited no favorable effect on the incidence of anal cancer.”

During the discussion period, Piketty and moderator Joel Palefsky attributed the increased incidence to the fact that potent HIV therapy has kept people with HIV alive long enough to progress to anal cancer.

Piketty and colleagues said their data “support the urgent need for developing anal cancer screening programs for HIV-infected individuals,” whether they are untreated or using antiretroviral therapy.

References

Piketty, C, et al. Dramatic increase in the incidence of anal cancer despite HAART in the French hospital database on HIV. Sixteenth International AIDS Conference, Toronto, abstract TUAB0305, 2006.