Background The incidence of anal cancer has increased in recentdecades, particularly among women. To identify underlying riskfactors, we conducted a population-based casecontrolstudy in Denmark and Sweden.
Methods We conducted telephone interviews with 324 women and93 men in whom invasive or in situ anal cancer was diagnosedbetween 1991 and 1994, 534 controls with adenocarcinoma of therectum, and 554 population controls. The interviews covereda wide spectrum of possible risk factors for anal cancer. Oddsratios were calculated by logistic regression. Specimens ofanal-cancer tissue and samples of rectal adenocarcinomas weretested for human papillomavirus (HPV) DNA with the polymerasechain reaction.
Results Multivariate analysis revealed consistent and statisticallysignificant associations between measures of sexual promiscuityand the risk of anal cancer in both men and women. There wasa significant trend toward an association between higher numbersof partners of the opposite sex in women (P<0.001) and men(P<0.05) and strong associations with a variety of venerealdiseases. In women, receptive anal intercourse, particularlybefore the age of 30 years, and venereal infections in the partnerwere also associated with an increased risk (odds ratios, 3.4and 2.4, respectively). Fifteen percent of the men with analcancer reported having had homosexual contact, as compared withnone of the controls (P<0.001). High-risk types of HPV, notablyHPV-16, were detected in 84 percent of the anal-cancer specimensexamined, whereas all rectal-adenocarcinoma specimens testedwere negative for HPV.
Conclusions Our study provides strong evidence that a sexuallytransmitted infection causes anal cancer. The presence of high-risktypes of HPV, notably HPV-16 (which is known to cause cancerof the cervix), in the majority of anal-cancer tissue specimenssuggests that most anal cancers are potentially preventable.(N Engl J Med 1997;337;1350-8.)
Source Information
From the Department of Epidemiology Research, Danish Epidemiology Science Center, Statens Serum Institut, Copenhagen, Denmark (M.F., J.W., M.M.); the Department of Oncology, University Hospital, Uppsala, Sweden (B.G.); the Department of Pathology, Section for Molecular Pathology, University Hospital, Vrije Universiteit, Amsterdam (A.J.C.B., C.J.L.M.M., J.M.M.W.); the Department of Surgery, Ersta Hospital, Stockholm, Sweden (S.G.); the Oncology Department of Southern Stockholm, Huddinge University Hospital, Stockholm, Sweden (C.S.); the Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden (H.-O.A.); and the Department of Epidemiology and Harvard Center for Cancer Prevention, Harvard University, Boston (H.-O.A.).
Address reprint requests to Dr. Frisch at the Department of Epidemiology Research, Danish Epidemiology Science Center, Statens Serum Institut, 2300-Copenhagen S, Denmark.
Li, A H, Phanuphak, N, Sahasrabuddhe, V V, Chaithongwongwatthana, S, Vermund, S H, Jenkins, C A, Shepherd, B E, Teeratakulpisarn, N, van der Lugt, J, Avihingsanon, A, Ruxrungtham, K, Shikuma, C, Phanuphak, P, Ananworanich, J
(2009). Anal squamous intraepithelial lesions among HIV positive and HIV negative men who have sex with men in Thailand. Sex. Transm. Infect.
85: 503-507
[Abstract][Full Text]
Vajdic, C M, van Leeuwen, M T, Jin, F, Prestage, G, Medley, G, Hillman, R J, Stevens, M P, Botes, L P, Zablotska, I, Tabrizi, S N, Grulich, A E
(2009). Anal human papillomavirus genotype diversity and co-infection in a community-based sample of homosexual men. Sex. Transm. Infect.
85: 330-335
[Abstract][Full Text]
Ferris, D. G., Waller, J. L., Miller, J., Patel, P., Price, G. A., Jackson, L., Wilson, C.
(2009). Variables Associated With Human Papillomavirus (HPV) Vaccine Acceptance by Men. J Am Board Fam Med
22: 34-42
[Abstract][Full Text]
Batty, H. P.
(2008). What about the boys?. cfp
54: 1375-1375
[Full Text]
Madsen, B. S., van den Brule, A. J.C., Jensen, H. L., Wohlfahrt, J., Frisch, M.
(2008). Risk Factors for Squamous Cell Carcinoma of the Penis--Population-Based Case-Control Study in Denmark. Cancer Epidemiol. Biomarkers Prev.
17: 2683-2691
[Abstract][Full Text]
Uronis, H. E., Bendell, J. C.
(2007). Anal Cancer: An Overview. The Oncologist
12: 524-534
[Abstract][Full Text]
Nordenvall, C, Nyren, O, Ye, W
(2006). Elevated anal squamous cell carcinoma risk associated with benign inflammatory anal lesions. Gut
55: 703-707
[Abstract][Full Text]
Bodaghi, S., Wood, L. V., Roby, G., Ryder, C., Steinberg, S. M., Zheng, Z.-M.
(2005). Could Human Papillomaviruses Be Spread through Blood?. J. Clin. Microbiol.
43: 5428-5434
[Abstract][Full Text]
Bodaghi, S., Yamanegi, K., Xiao, S.-Y., Da Costa, M., Palefsky, J. M., Zheng, Z.-M.
(2005). Colorectal Papillomavirus Infection in Patients with Colorectal Cancer. Clin. Cancer Res.
11: 2862-2867
[Abstract][Full Text]
Ponz de Leon, M, Benatti, P, Borghi, F, Pedroni, M, Scarselli, A, Di Gregorio, C, Losi, L, Viel, A, Genuardi, M, Abbati, G, Rossi, G, Menigatti, M, Lamberti, I, Ponti, G, Roncucci, L
(2004). Aetiology of colorectal cancer and relevance of monogenic inheritance. Gut
53: 115-122
[Abstract][Full Text]
Hemminki, K., Li, X.
(2003). Lifestyle and Cancer: Effect of Widowhood and Divorce. Cancer Epidemiol. Biomarkers Prev.
12: 899-904
[Abstract][Full Text]
Frisch, M., Smith, E., Grulich, A., Johansen, C.
(2003). Cancer in a Population-based Cohort of Men and Women in Registered Homosexual Partnerships. Am J Epidemiol
157: 966-972
[Abstract][Full Text]
Walker, F., Kermorgant, S., Darai, E., Madelenat, P., Cremieux, A. C., Henin, D., Lehy, T.
(2003). Hepatocyte Growth Factor and c-Met in Cervical Intraepithelial Neoplasia: Overexpression of Proteins Associated with Oncogenic Human Papillomavirus and Human Immunodeficiency Virus. Clin. Cancer Res.
9: 273-284
[Abstract][Full Text]
Sobhani, I., Walker, F., Aparicio, T., Abramowitz, L., Henin, D., Cremieux, A. C., Soule, J. C.
(2002). Effect of Anal Epidermoid Cancer-related Viruses on the Dendritic (Langerhans') Cells of the Human Anal Mucosa. Clin. Cancer Res.
8: 2862-2869
[Abstract][Full Text]
Esiashvili, N., Landry, J., Matthews, R. H.
(2002). Carcinoma of the Anus: Strategies in Management. The Oncologist
7: 188-199
[Abstract][Full Text]
Schecter, W. P.
(2001). Human Immunodeficiency Virus and Malignancy: Thoughts on Viral Oncogenesis. Arch Surg
136: 1419-1425
[Full Text]
Carter, J. J., Madeleine, M. M., Shera, K., Schwartz, S. M., Cushing-Haugen, K. L., Wipf, G. C., Porter, P., Daling, J. R., McDougall, J. K., Galloway, D. A.
(2001). Human Papillomavirus 16 and 18 L1 Serology Compared across Anogenital Cancer Sites. Cancer Res.
61: 1934-1940
[Abstract][Full Text]
Ryan, D. P., Compton, C. C., Mayer, R. J.
(2000). Carcinoma of the Anal Canal. NEJM
342: 792-800
[Full Text]
Frisch, M., Glimelius, B., Wohlfahrt, J., Adami, H.-O., Melbye, M.
(1999). Tobacco Smoking as a Risk Factor in Anal Carcinoma: an Antiestrogenic Mechanism?. JNCI J Natl Cancer Inst
91: 708-715
[Abstract][Full Text]
Moscicki, A.-B., Hills, N. K., Shiboski, S., Darragh, T. M., Jay, N., Powell, K., Hanson, E., Miller, S. B., Farhat, S., Palefsky, J.
(1999). Risk Factors for Abnormal Anal Cytology in Young Heterosexual Women. Cancer Epidemiol. Biomarkers Prev.
8: 173-178
[Abstract][Full Text]
Frisch, M., Fenger, C., van den Brule, A. J. C., Sorensen, P., Meijer, C. J. L. M., Walboomers, J. M. M., Adami, H.-O., Melbye, M., Glimelius, B.
(1999). Variants of Squamous Cell Carcinoma of the Anal Canal and Perianal Skin and Their Relation to Human Papillomaviruses. Cancer Res.
59: 753-757
[Abstract][Full Text]
Vernon, S. D., Unger, E. R., Reeves, W. C., Frisch, M., Adami, H.-O., Melbye, M., Ellerbrock, T. V., Kuhn, L., Wright, T. C.
(1998). Human Papillomaviruses and Anogenital Cancer. NEJM
338: 921-922
[Full Text]
(1998). Anal Carcinoma Is an STD. Journal Watch Dermatology
1998: 11-11
[Full Text]
Shah, K. V.
(1997). Human Papillomaviruses and Anogenital Cancers. NEJM
337: 1386-1388
[Full Text]