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Incidence
The predicted lifetime risk for an uncircumcised man has been estimated as 1 in 600 in the USA and 1 in 900 in Denmark [189]. Penile cancer accounts for approx. 0.2% of all malignancies in men in the USA and 0.1% of cancer deaths, the 5-year survival rate being 50% [11]. Mortality rate is 25-33% [189, 216]. The annual incidence of cancer of the penis in the USA is approx. 1 per 100,000 men per year [11, 80]. (In comparison, cervical cancer is 10 times higher [see below], prostate cancer is 100 times higher, and fatal heart attack is 200 times higher.) Statistics on the American Cancer Society web page point to 1,470 new cases of penile cancer in 2005, with 270 deaths [11, 168]. Neonatal circumcision virtually abolishes the risk [313]. The rate data in the USA has to be viewed in the context of the high proportion of circumcised men in the USA, especially in older age groups, and the age group affected (mean age at presentation = 60 years), where older men represent only a portion of the total male population. Thus the incidence of 1 in 100,000 men per year of life translates to 75 in 100,000 during each man's lifetime (assuming an average life expectancy of 75 years). However, penile cancer occurs almost entirely in uncircumcised men. If we assume that these represent 30% of males in the USA, the chance an uncircumcised man will get it would be (very approximately) 75 per 30,000 = 1 in 400. Perhaps not surprisingly this accords with the incidence that is actually seen (as stated at the beginning of this paragraph). In 5 major series in the USA, starting in 1932 [402], not one man with invasive penile cancer had been circumcised neonatally [216], i.e., this disease is almost completely confined to uncircumcised men. In fact penile cancer is so rare in a man who had been circumcised in infancy, that when it does occur it can even be the subject of a published case report [175]. The finite residual risk appears to be greater in those circumcised after the newborn period, but still less than the uncircumcised. Lifetime risk in the total population of circumcised men is only 1 in 50,000 to 1 in 12,000,000 [391, 392]. In a study of 213 cases in California only 2 of 89 men with of invasive penile cancer was circumcised in infancy, so that uncircumcised men were stated to have 22 times the risk [317, 318]. Of 118 with the localized, and thus more easily curable, variety of penile cancer, namely carcinoma in situ (which is not lethal), only 16 had been circumcised as newborns, i.e., incidence was 3-fold higher in the uncircumcised [216, 317, 318]. Overall there were 50,000 cases of penile cancer in the USA from 1930 to 1990 and these resulted in 10,000 deaths. Only 10 of these cases were in circumcised men [311], and these had been circumcised later in life. In Denmark (circumcision rate = 2%), penile cancer has been decreasing steadily [115] in parallel with an increase in indoor bathrooms. Urban unmarried men were more likely to get it. Since the rate of penile cancer in Denmark is lower than in the USA other factors besides circumcision are also at work in these climatically, genetically and culturally different countries. The statistics for Denmark have been used by anti-circ advocates to draw a sweeping and fallacious conclusion about lack of circumcision per se in penile cancer. The Danish themselves have concluded that although their uncircumcised men are at lower risk, this is only 1 in 900 as opposed to 1 in 600 in the USA, as stated above [189]. A study in Spain concluded that "circumcision should be performed in childhood [as a] prophylactic [to penile cancer] [305]. As a historical point of interest, Diego Rivera, the famous Mexican muralist, reportedly died of penile cancer. In underdeveloped countries the incidence is higher: approx. 3-10 cases per 100,000 per year [189]. In those underdeveloped countries where circumcision is not routinely practiced, such as South America and parts of Africa, it can be ten times more common than in developed countries, representing 10–22% of all male cancers [11, 139, 239]. In Uganda and some other African countries it is the most common malignancy in males, leading to calls for greater circumcision [91]. Enormous differences are, moreover, seen in third world nations such as Nigeria (circumcised: low rate) when compared with Uganda, Puerto Rico [404] and Brazil [367], where most males are uncircumcised. In Australia there were 78 cases in 2000, and over the decade to that year cases averaged approx. 60 per year [21]. Of these, 4% were in their 30s, 14% in their 40s, 15% in their 50s, 22% in their 60s, 31% in their 70s, and was 12% in those aged over 80 [21]. One in four died as a result, the rate being higher in older men. The incidence figures were 0.8 per 100,000 population [21], i.e., was similar to the USA, and was also similar in each state of Australia. Life-time (age 0–74) risk was estimated as 1 in 1,574 males [21]. As in the USA, a majority of older men in Australia are circumcised, so any future decline in proportion of uncircumcised males in the Australian population will be expected to be accompanied by an escalation in the rate of penile cancer. As mentioned earlier, the rate of cervical cancer is 10 times higher, with 745 cases in Australia in 2000 (incidence 7.6 per 100,000) and 265 deaths [21]. In Israel, where almost all males are circumcised, the rate of penile cancer is extremely low: 0.1 per 100,000, i.e., is 1/10th that of Denmark [404]. Cause Cancer of the penis presents as carcinoma in situ or invasive penile cancer. The proportion of each of these is roughly equal (45% vs 55% in the USA). Invasive penile cancer is lethal, whereas carcinoma in situ is comparatively benign. Moreover, the former is not necessarily a continuum of the latter [82]. Human papillomavirus (HPV) is present in most basaloid and warty carcinomas which comprise 50% of cases [139]. Similarly, in women, half of all vulvar carcinomas are HPV-positive (cf. the close to 100% positivity for high-risk HPVs in cervical cancer). High-risk HPV is found more frequently in verrucous carcinomas than giant condylomas (which are caused by low-risk HPV) and keratinizing and verrucous carcinomas are HPV positive in one-third of cases [139]. Thus high risk HPV (types 16, 18 and a large number of rarer types) are found in a large proportion of cases and there is good reason to suspect that they are involved in the causation of penile cancer [229], i.e, the same virus is responsible as is the case for virtually all cases of cervical cancer in women (see below). The distribution of HPV on the penis has been reported as 28% foreskin, 24% shaft, 17% scrotum, 16% glans and 6% urine [375]. HPVs, notably high-risk types, are more common in uncircumcised males [34, 60, 190, 200, 244]. In a large study published in the New England Journal of Medicine in 2002 HPV was detected in 19.6% of 847 uncircumcised men, but only 5.5% of 292 circumcised men (overall odds ratio after adjusting for potential confounding factors = 0.37) [60]. In a study of healthy military men in Mexico the odds ratio for persistent HPV infection was 10 times higher in uncircumcised compared with circumcised [200]. The high-risk types of HPV produce flat warts that are normally only visible by application of dilute acetic acid (vinegar) to the penis. The majority of infections are subclinical, being more prevalent in uncircumcised men with balanoposthitis [190]. The data on high-risk HPVs should not be confused with the incidence figures for genital warts, which are large and readily visible, and are caused by the relatively benign HPV types 6 and 11 [180]. Smegma (found only under the foreskin) was implicated in an early study [278]. It is not clear, however, what component was responsible, and could have been HPV present in the smegma. Interestingly, 93% of men whose female partner was positive for early signs of cervical cancer (cervical intra-epithelial neoplasia, CIN) had the male equivalent, penile intra-epithelial neoplasia (PIN) [23]. This reflects the fact that the disease, via HPV, is sexually transmitted. Oncogenic HPV was present in 75% of patients with PIN grade I, 93% with PIN grade II and 100% of PIN grade III, which is one step before penile cancer itself [23]. Moreover, the rate of PIN was 10% in uncircumcised men cf. only 6% in circumcised men [23]. HPV DNA was found in 80% of tumor specimens, with 69% being the high-risk type 16 [82]. Condom use lowers HPV infection, as reported in a study of 393 men [34]. Phimosis is strongly associated with invasive penile carcinoma (adjusted odds ratio = 16 in one study [359] and 11 in another [82]). Other factors, such as smoking (4.5-fold increase in risk [82]), poor hygiene and other STIs have also been suspected as contributing to penile cancer as well [33, 216], but it would seem that lack of circumcision is the primary prerequisite, with such other factors adding to the risk in the uncircumcised man. Indeed, there is no scientific evidence that improved penile hygiene is effective in reducing the risk in an uncircumcised man [234]. It has been concluded that circumcision in early childhood, by eliminating phimosis, may help prevent penile cancer [82]. Treatment Complete or partial surgical amputation is the traditional treatment. Radiation is an alternative (or additional) therapy and in early-stage disease can preserve function of the organ. In a retrospective study in Switzerland of 41 consecutive patients with non-metastatic invasive carcinoma of the penis 44% underwent surgery (to remove all or part of the penis, as well as lymph nodes in one third), followed by radiation therapy (in three-quarters) and the rest (56%) had just radiation therapy [410]. Over the median 70 months of follow-up 63% relapsed. For all patients 5-year survival rate was 57% and 10-year survival was 38%. Local relapse rate was lower in those who underwent surgery. However, there was no difference in survival when compared with radiation therapy, either alone, or in conjunction with salvage surgery. A recent review has emphasized the role of lack of circumcision and poor prognosis, as well as providing an update on treatment options [52]. The psychosexual implications to a man are, understandably, not inconsequential [255]. The fact that, as is the case for breast cancer, the sex-related organ is often surgically removed adds to the devastating physical and emotional impact of penile cancer. But the 5-year survival rate is lower [289]. It would be cold comfort to a man so afflicted to know that his disease could almost certainly have been prevented had he been circumcised in infancy. Cost Financial considerations are, moreover, not inconsiderable. In the USA it was estimated that the cost for treatment and lost earnings in a man of 50 with cancer, even back in 1980, was $103,000 [152]. The amount today is very much higher. Deaths from penile cancer vs. circumcision In Australia between 1960 and 1966 there were 78 deaths from cancer of the penis and 2 from circumcision. (Circumcision fatalities today are virtually unknown in hospital settings.) At the Peter McCallum Cancer Institute 102 cases of penile cancer were seen between 1954 and 1984, with twice as many in the latter decade compared with the first [306]. Moreover, several authors have linked the rising incidence of penile cancer to a decrease in the number of neonatal circumcisions [81, 306]. It would thus seem that "prevention by circumcision in infancy is the best policy". Indeed it would be an unusual parent who did not want to ensure their child was completely protected by this simple procedure. Prostate Cancer Prostate cancer accounts for one-quarter of all new cancers in males and 7% of deaths [21]. Uncircumcised men have more than twice the incidence of prostate cancer compared with circumcised [16, 103, 287], and prostate cancer is rare amongst Jews [9]. No association has been seen between rate of prostate cancer and rate of cervical cancer in different geographic localities [297]. However, in a study of 20,243 men in Finland, infection with HPV18 was associated with a 2.6-fold increase in risk of prostate cancer (P < 0.005) [88]. For HPV16 the increased risk was 2.4-fold. This is similar to the increased penile HPV infection in uncircumcised men [60]. Ascending passage of the HPV to the prostate could be causative. According to the American Cancer Society 1 in 6 men get prostate cancer during their lifetime. If uncircumcised men have double the risk, and assuming half of the men in the at-risk age group are uncircumcised, then risk in an uncircumcised man would be 1 in 4, and risk in a circumcised man would be 1 in 8 (i.e., circumcision prevents prostate cancer in 33% minus 11% = 22% of men). This means that in the USA the 2 million circumcisions performed each year prevent approx. 22% of 2M = 440,000 cases of prostate cancer over the average 76 year lifetime. Each case costs on average US$13,823 just for radiation therapy [136], meaning a total extra cost of US$6 billion. Add to this the combined cost for terminal care of the 41,000 who die of prostate cancer each year of $24,660 per patient [136] (= $1 billion), the overall annual cost is over US$7 billion. This compares with US$390 million per year in total for a high-end estimate of physician + hospital costs for a neonatal circumcision in the USA of $195 [365]. [These calculations were assisted by Jake Waskett, Joshua Amos and Tatsuo Bradio (unpublished).] |
