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IN RESPONSE
Submit responseIN RESPONSE:
We appreciate the comments of Klausner and others in their recent letter and for their efforts to draw attention to this important issue. The authors of the letter are correct – the incidence of anal cancer is not decreasing. Indeed, published data show that invasive anal cancer incidence 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 used age-adjusted incidence rates from 1973-1999 (beginning prior to the period analyzed by Klausner 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 population in 1973-78, to 4.5 per 100,000 by 1991-95 (2). Klausner and colleagues’ data are consistent with Cress’ data for the time period they reviewed (beginning in 1988), and actually show a further increase in incidence of invasive anal cancer to almost 10 per 100,000 population by 2004-2005.
The increase in anal cancer incidence is even more pronounced in high -risk populations such as HIV-positive individuals − 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 others demonstrated that after adjustment for age at AIDS diagnosis, race, risk group, sex, calendar year, HAART use, and HAART era, the risk of anal cancer was statistically significantly higher in the HAART era (RH = 2.74) (3). 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 entirely possible − as Klausner and colleagues postulate − that the rates of invasive anal cancer could have been even higher if there was no screening and treatment of AIN 3 in this population.
However this is speculative and as Klausner and colleagues themselves state in the letter, “This ecologic analysis does not prove that screening is ineffective.” One could use ecologic 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 of 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 (4).
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 impact 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 of individuals, i.e. those with HIV infection, to most quickly determine the impact of screening. Studies will also need to be conducted to determine the acceptability and tolerability of treatment for AIN. If the prophylactic quadrivalent HPV vaccine is approved by the FDA for men, 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 HPV infection and potential anal cancer precursor lesions among MSM and 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.
REFERENCES
1. Joseph DA, Miller JW, Wu X, et al. Understanding the burden of human papillomavirus-associated anal cancers in the US. Cancer. 2008;113(10 Suppl):2892-900.
2. Cress RD, Holly EA. Incidence of anal cancer in California: increased incidence among men in San Francisco, 1973-1999. Prev Med. 2003;36(5):555-60.
3. Hessol NA, Pipkin S, Schwarcz S, Cress RD, Bacchetti P, Scheer S. The impact of highly active antiretroviral therapy on non-AIDS-defining cancers among adults with AIDS. Am J Epidemiol. 2007;165(10):1143-53.
4. Chin-Hong PV, Berry JM, Cheng SC, et al. Comparison of patient- and clinician-collected anal cytology samples to screen for human papillomavirus-associated anal intraepithelial neoplasia in men who have sex with men. Ann Intern Med. 2008;149(5):300-6.
Conflict of Interest:
None declared
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Anal Cancer Screening: Taking a Step Back
Submit responseWe read with interest Chin-Hong et al.’s study comparing techniques to detect anal intraepithelial neoplasia (AIN) among men who have sex with men (MSM)(1). A more pressing question is whether sufficient evidence of effectiveness, in terms of reducing anal cancer morbidity or mortality, exists to support anal cancer screening. It does not.
No prospective studies, including randomized controlled trials (RCTs), have assessed anal cancer screening effectiveness(2). Instead, screening proponents have cited indirect evidence, including analogy to cervical cancer screening, to advocate for routine screening among certain populations, including MSM(2,3). As screening proponents rightly note, RCTs of Papanicolaou smears for cervical cancer prevention were never conducted; evidence of effectiveness is based on data correlating increased screening and decreased cancer incidence(2).
In San Francisco, anal cancer screening has been offered at health care provider practices since the late 1990s. Reporting of invasive anal cancer and anal intraepithelial neoplasia 3 (sometimes called in situ carcinoma) is legally mandated in California. We used data from the California Cancer Registry to examine trends in AIN 3 lesions and invasive anal squamous cell cancer (SCC) reported among non-Hispanic white male residents of San Francisco County during 1988–2005(4). As displayed in the figure (http://www.sfcityclinic.org/misc/Katzk_anal_cancer_Annals_letter_ver14.2_final_graph.pdf),age-adjusted incidence of invasive anal SCC was stable from the mid-1990s, whereas AIN 3 incidence substantially increased during 2001–2005, compared with previous years. Anal cancer mortality rates are not reliable for this population because fewer than five deaths occur yearly from anal cancer.
These data demonstrate that screening was associated with increasing detection of AIN 3 lesions but not decreased incidence of invasive cancer. Biologic or anatomic differences between the anal canal and the cervix might render anal cancer screening less effective than cervical cancer screening. Negative consequences of anal cancer screening, including anxiety, fear, and depression after receiving abnormal results, and procedural complications (5) might also affect the cost-benefit ratio unfavorably.
This ecologic analysis does not prove that screening is ineffective. Invasive cancer incidence might have increased without screening; insufficient numbers or types of patients might have been screened; insufficient time might have elapsed to detect a reduction in incidence; or ecologic analysis might lack sensitivity to detect incidence changes among specific populations at high risk.
Only an RCT involving numerous subjects can—and, we hope, ultimately will—provide conclusive effectiveness data(2). Meanwhile, given screening’s costs and consequences, sufficient evidence does not exist to support routine anal cancer screening for MSM.
(1) STD Prevention and Control Services, San Francisco Department of Public Health, San Francisco, CA
(2) Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, GA
(3) Northern California Cancer Center, Fremont, CA
(4) Stanford University School of Medicine, Palo Alto, CA
(5) San Francisco Department of Public Health, San Francisco, CA
(6) Department of Medicine, University of California at San Francisco, San Francisco, CA
Note
The cancer incidence data used in this study were supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N01-PC-54404 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention’s National Program of Cancer Registries, under agreement 1U58DP00807-01 awarded to the Public Health Institute. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the State of California, the California Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their contractors and subcontractors. Endorsement by any of those agencies is not intended nor should be inferred.
References
1. Chin-Hong P, Berry JM, Cheng S-C, et al. Comparison of patient- and clinician-collected anal cytology samples to screen for human papillomavirus-associated anal intraepithelial neoplasia in men who have sex with men. Ann Intern Med. 2008;149:300-6.
2. Chiao EY, Giordano TP, Palefsky JM, Tyring S, El Serag H. Screening HIV-infected individuals for anal cancer precursor lesions: a systematic review. Clin Infect Dis. 2006; 43:223-33.
3. Palefsky J, Hecht J, Riggs J, Scarce M. Needed: routine HPV vaccines and Pap smears for gay and bisexual men. The San Francisco Chronicle. 2007 Apr 24; Sect. B:7.
4. California Department of Public Health, Cancer Surveillance and Research Branch. California cancer registry. SEER*stat database: incidence — California, April 2008 (1988–2006). NCHS population estimates for 1990–2006; Benchmarked 1988–1989 DOF population estimates July 2007. Available at: http://www.ccrcal.org. Accessed September 22, 2008.
5. Pineda CE, Berry JM, Jay N, Palefsky JM, Welton ML. High-resolution anoscopy targeted surgical destruction of anal high-grade squamous intraepithelial lesions: a ten-year experience. Dis Colon Rectum. 2008;51:829-35.
Conflict of Interest:
None declared