Is There a Proven Link Between Anal Cancer Screening and Reduced Morbidity or Mortality?

IN RESPONSE:

We appreciate Dr. Katz and colleagues' comments and their efforts to draw attention to this important issue. They are correct: The incidence of anal cancer is not decreasing. Indeed, published data show that the incidence of invasive anal cancer is increasing in men and women worldwide. In a recent review of 39 population-based registries in the United States between 1998 and 2003, invasive anal cancer increased 2.6% per year on average (1). Using California Cancer Registry data, Cress and Holly (2) used age-adjusted incidence rates from 1973 to 1999 (beginning before the period analyzed by Dr. Katz and colleagues) to show that, among Hispanic and non-Hispanic white men in San Francisco County, age-adjusted rates of invasive anal cancer tripled from 1.5 per 100 000 persons in 1973 to 1978 to 4.5 per 100 000 persons in 1991 to 1995. Dr. Katz and colleagues' data are consistent with Cress and Holly's data for the period they reviewed (beginning in 1988) and show a further increase in incidence of invasive anal cancer to almost 10 per 100 000 persons by 2004 to 2005.

The increase in anal cancer incidence is even more pronounced in high-risk populations, such as HIV-positive persons, despite the widespread use of highly active antiretroviral therapy (HAART). Matching data from the San Francisco AIDS registry and the California Cancer Registry, Hessol and colleagues (3) demonstrated that after adjustment for age at AIDS diagnosis, race, risk group, sex, calendar year, HAART use, and HAART era, the risk for anal cancer was significantly higher in the HAART era (relative hazard, 2.74). Given that HAART was not associated with a decline in the incidence of invasive anal cancer, even with the limited number of people screened and treated, it is possible—as Dr. Katz and colleagues postulate—that the rates of invasive anal cancer could have been even higher if there was no screening for and treatment of AIN 3 in this population.

However, this is speculative and, as Dr. Katz and colleagues state, “This ecological analysis does not prove that screening is ineffective.” One could use ecological data to show a population-level impact of screening on reducing cancer incidence, but this kind of analysis will be less sensitive to demonstrate a true effect if there really was one, unless screening is relatively common in the population at highest risk for disease. Unfortunately, this is not the case. In our community-based sample of men who have sex with men in San Francisco County, a population for which we have advocated systematic screening, only 7% previously underwent anal cancer screening.

Overall, the evidence points to an increase in invasive anal cancer in men and women in the general population. In the absence of widespread systematic anal cancer screening (even in San Francisco), it is difficult to use population-based cancer registry data to discount the benefit of anal cancer screening. We strongly agree that more studies are needed to determine the effect of screening on a population level, similar to what was done with cervical cancer screening. In this case, we would focus on the highest-risk group—those with HIV infection—to most quickly determine the impact of screening. Studies are also needed to determine the acceptability and tolerability of treatment of AIN. If the prophylactic quadrivalent human papillomavirus vaccine is approved for men by the U.S. Food and Drug Administration, additional studies will be needed to determine the effectiveness of the vaccine on anal cancer and associated precursor lesions. In the interim, given the high prevalence of anal human papillomavirus infection and potential anal cancer precursor lesions among men who have sex with men and among HIV-positive men and women, we believe that sufficient evidence already exists for screening populations at high risk for anal cancer. We believe that investment in capacity building is most needed, with continued training of personnel to provide education to patients and providers and to conduct high-resolution anoscopy and treatment.