Male Circumcision, Penile Human Papillomavirus Infection, and Cervical Cancer in Female Partners

Little is known about the effect of male circumcision on the risk of acquiring human papillomavirus (HPV). HPV causes genital warts in men and women, and it has been linked to cancers of the cervix, vulva, vagina, anus and penis. Up to 99 percent of all cervical cancer cases may be attributed to infection by oncogenic HPV genotypes. From 1985 to 1993, the International Agency for Research on Cancer has performed seven case-control studies of cervical cancer in several countries. Researchers used data from these studies to assess the effect of male circumcision on the risk of genital HPV infection in the men themselves and the risk of cervical cancer in their sexual partners. Five studies involved invasive cervical cancer, and two studies involved cervical carcinoma in situ.

Female patients had newly diagnosed, histologically confirmed cervical carcinoma in situ or invasive cervical cancer. Control women were recruited from the general population in the two population-based studies of invasive cancer, and from the same hospitals as the patients in the other hospital-based studies. Subjects and controls were frequency-matched according to age. Eligible men were the husbands or stable partner (having had regular sexual intercourse with the woman for at least six months) of the women enrolled in each of these studies. A clinician confirmed the circumcision status in the case of 794 of the 815 men (94.7 percent) recruited; the status of four men was uncertain. On the basis of this high degree of reliability, the self-reported circumcision status was used for all analyses.

Of the 3,790 women, (1,896 women with cervical cancer and 1,894 controls) who were enrolled, 2,800 (1,329 women with cancer, 1,471 controls) reported having a husband or stable partner. A total of 984 of the 1,329 partners of women with cervical cancer (74 percent) and 937 of the 1,471 partners of control women (63.7 percent) were interviewed. Of these, 807 partners of patients (82 percent of those interviewed) and 717 partners of control women (76.5 percent) provided cytologic specimens, of which 610 (75.6 percent) and 533 (74.3 percent), respectively, yielded a valid PCR assay result.

HPV DNA was detected in 182 of the 1,139 penile specimens (16 percent): in 19.6 percent of uncircumcised men (166 of 847) and 5.5 percent of circumcised men (16 of 292). Circumcised men had a comparatively lower prevalence of HPV infection in all subgroups defined according to base-line characteristics. There was an inverse association between circumcision and the risk of HPV infection in all studies, whether or not the female partner had cervical HPV or cancer diagnosis.

Male circumcision was associated with a moderate, but non-significant, decrease in the female partner's risk of cervical cancer. The inverse relation between circumcision and risk of cervical cancer was stronger and significant in the case of women with high risk sexual partners who engaged in practices known to increase the risk of HPV exposure, such as having had intercourse before the age of 17 years, having had six or more partners, and having a history of contact with prostitutes. Tests for an interaction between circumcision status, the male and the male partner's number of sexual partners and between circumcision status and the risk index were significant.

Circumcision may reduce the risk of cervical cancer in female sex partners for several plausible reasons, according to the authors. First, circumcision is associated with a significant decrease in the risk of penile HPV infection. Second, penile HPV is associated with a fourfold increase in the risk of cervical HPV infection. Third, cervical HPV infection is associated with a 77-fold increase in the risk of cervical cancer. Thus, the authors concluded, circumcision can be considered an important cofactor in the natural history of HPV infection. The findings are consistent with other studies that male circumcision is associated with reduced risk of HIV infection. Further study is needed to determine whether routine circumcision can reduce the risks of HIV and HPV infections and other STDs.

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