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A number of studies have documented higher rates of cervical cancer in women who have had one or more male sexual partners who were uncircumcised. Whereas the earlier studies were somewhat equivocal the evidence from a recent large international study, to be discussed later, now provides overwhelming evidence of the link between lack of male circumcision and cervical cancer in the female sexual partner.
So-called 'high-risk' HPV types 16, 18 and some rarer forms are responsible for virtually every case of cervical cancer [273, 369, 370]. These same high-risk HPVs also cause penile intra-epithelial neoplasia (PIN), which is the precursor to penile cancer and is the male equivalent of cervical intra-epithelial neoplasia (CIN), which is the precursor to cervical cancer. (These days `CIN' is more often referred to as `squamous intra-epithelial lesion' - SIL - which can be of high or low grade, thus `HSIL' or `LSIL'.) In a study published in the New England Journal of Medicine in 1987 it was found that women with cervical cancer were more likely to have partners with PIN [35]. A study in 1994 found that in women with CIN, PIN was present in the male partner in 93% of cases [23]. This is consistent with the known sexual transmission of this cancer-causing virus. The abnormality (CIN / SIL) may progress to cancer or, more often, it will go away. Thus co-factors are suspected. Interestingly, smegma (the film of bacteria, secretions and other material under the foreskin), obtained from human and horse was shown to be capable of producing cervical cancer in mice in one study [275], but not in another [288]. Differences in exposure time in each study could have contributed to this difference.
In 2002, a large, well-designed multinational study by the International Agency for Research on Cancer published in the New England Journal of Medicine has irrefutably implicated the foreskin in cervical cancer [60]. This involved 1913 couples in 5 global locations in Europe , Asia and South America . Penile HPV was found in 20% of uncircumcised, but only 5% of circumcised men (odds ratio = 0.37). The women were more 5.6 times more likely to have cervical cancer if their partner was uncircumcised. This was seen in monogamous women whose male partner had had 6 or more sexual partners (adjusted odds ratio = 0.42), but circumcision was also protective in women whose partner had an intermediate sexual behavior risk index (odds ratio = 0.50). Penile HPV infection was associated with a 4-fold increase in the risk of cervical HPV infection in the female partner, and cervical HPV infection was associated with a 77-fold increase in the risk of cervical cancer. In an accompanying editorial it was suggested that "reduction in risk among female partners of circumcised as compared with uncircumcised men may well be more substantial than reported" in this study [1].