Incidence The predicted lifetime risk of penile cancer for an uncircumcised man has been estimated as 1 in 600 in the USA and 1 in 900 in Denmark [Kochen & McCurdy, 1980]. Penile cancer accounts for less than 1% of all malignancies in men in the USA and 0.1% of cancer deaths, the 5-year survival rate being approx. 50% [American, 2005a]. Mortality rate is 25-33% [Kochen & McCurdy, 1980; Maden et al., 1993]. The annual incidence of cancer of the penis in the USA is approx. 1 per 100,000 men per year [Crawford et al., 1988; American, 2005a]. (In comparison, cervical cancer incidence is 10 times higher [see below], breast cancer is 60 times higher, prostate cancer is 100 times higher, and fatal heart attack is 200 times higher.) Statistics on the American Cancer Society web page point to 1,280 new cases of penile cancer in 2007, with 290 deaths [American, 2007b]. The incidence of primary malignant penile cancer in the USA from 1973 to 2002 was 0.69 per 100,000, decreasing over the decades from 0.84 to 0.58 per 100,000 [Barnholtz-Sloan et al., 2007]. From 1998 to 2003, 4967 men were diagnosed with invasive squamous cell carcinoma in the USA (less than 1% of all new cancers in men; 0.81 cases per 100,000 men) [Hernandez et al., 2008a]. Squamous cell carcinoma is the most common type of penile cancer in the USA, representing 93% of all malignancies [Goodman et al., 2007]. In the USA, Hispanic men have the highest incidence (6.6 per million), then Black men (4.0 per million), White (3.9), American Indians (2.8) and Asian-Pacific Islanders (2.4) [Goodman et al., 2007]. For ages >85 y incidence was 47 and 36 per million in Hispanic and Black men, respectively [Goodman et al., 2007]. Owing to earlier diagnosis, incidence has been decreasing by 1.9% per year in Blacks and 1.2% in Whites [Goodman et al., 2007]. The majority (61%) were diagnoses at the localized stage. Regional differences were apparent. Another report gives figures for 1993 to 2002 of 1.01 per 100,000 for white Hispanics, 0.77 for Alaskan native/American Indians, 0.62 per 100,000 for Blacks and 0.51 for whites who are not Hispanic [Barnholtz-Sloan et al., 2007]. This correlates inversely with incidence of circumcision between these groups. Penile cancer is regarded as an "emerging problem" [Micali et al., 2006]. This large review also noted that "public health measures, such as prophylactic use of circumcision, have proven successful" [Micali et al., 2006]. Neonatal circumcision virtually abolishes the risk [Schoen, 1996]. 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 [Ries et al., 1998]), 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 in the first paragraph). In 5 major series in the USA, starting in 1932 [Wolbarst, 1932], not one man with invasive penile cancer had been circumcised neonatally [Maden et al., 1993], 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 [Kanik et al., 1997]. The finite residual risk appears to be greater in those circumcised after the newborn period, but still less than the uncircumcised. In this regard penile cancer in circumcised men (av. age 62) in Saudi Arabia (where circumcision is performed in older children) was associated with ritual, nonclassical, vigorous circumcision [Seyam et al., 2006]. Lifetime risk in the total population of circumcised men is only 1 in 50,000 to 1 in 12,000,000 [Wiswell, 1995; Wiswell, 1997a]. 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 a 22 times higher risk [Schoen et al., 2000b; Schoen et al., 2000c]. 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 [Maden et al., 1993; Schoen et al., 2000b; Schoen et al., 2000c]. A study in Louisiana found that only 2 of 45 penile cancer patients had been circumcised in infancy [Carver et al., 2002]. Circumcision later in life is much less effective [Tsen et al., 2001]. 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 [Schoen, 1991], and these had been circumcised later in life. In Denmark (circumcision rate = 2%), penile cancer has been decreasing steadily [Frisch et al., 1995] 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, dietarily and culturally different countries. The statistics for Denmark have been used by anti-circumcision 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 [Kochen & McCurdy, 1980]. A study in Spain concluded that "circumcision should be performed in childhood [as a] prophylactic [to penile cancer]" [Sanchez Merino et al., 2000]. As a historical point of interest, Diego Rivera, the famous Mexican muralist, who had multiple sexual partners over many years in a country where most men are uncircumcised, developed penile cancer [Schoen, 2007d]. He refused penectomy (surgical removal of the penis) and instead (as a Communist) went to the Soviet Union for radiation therapy. He died a painful death from the disease and the side effects of his therapy. In underdeveloped countries the incidence is higher: approx. 3-10 cases per 100,000 per year [Kochen & McCurdy, 1980]. In those underdeveloped countries where circumcision is not practiced routinely, 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 [Narayana et al., 1982; Gross & Pfister, 2004; American, 2005a]. In Uganda and some other African countries it is the most common malignancy in males, leading to calls for greater circumcision [Dodge & Linsell, 1963]. Enormous differences are, moreover, seen amongst third world nations according to circumcision rates. As well as Uganda, Puerto Rico [World., 1997], India and Brazil [Villa & Lopez, 1986; Favorito et al., 2008] most men are uncircumcised and penile cancer is very common. Brazil has one of the highest rates of penile cancer - 3-7 per 100,000 inhabitants, i.e., 6-14 per 100,000 males, comprising 2-6% of all male neoplasias, with 7% being seen in men aged less than 35 and 39% in men older than 66 [Favorito et al., 2008]. The uncircumcised made up 87% of cases. All tumors seen in men circumcised in childhood were low-grade, whereas 12% of those circumcised in adulthood had high-grade tumors [Favorito et al., 2008]. In Australia there were 67 cases in 2003, and over the decade to that year cases averaged 66 per year [Australian, 2004b]. Typical age distribution of cases is approx. 4% aged 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 [Australian, 2004a]. One in four died as a result, the rate being higher in older men. The annual incidence of penile cancer is 0.8 per 100,000 population [Australian, 2004a], 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 [Australian, 2004a]. As in the USA, over two-thirds of older men in Australia are circumcised, so any future decline in proportion of uncircumcised males in the Australian population will, by itself, be expected to be accompanied by an escalation in the rate of penile cancer. As mentioned earlier, the rate of cervical cancer is, in contrast, 10 times higher, with 725 cases in Australia in 2003 (incidence 9.1 per 100,000) and 212 deaths [Australian, 2007]. 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 [World., 1997; Solsona et al., 2004].















Cause: Role for human papillomavirus (HPV) infection 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 [Daling et al., 2005]. Human papillomavirus (HPV) is present in most basaloid and warty carcinomas which comprise 50% of cases [Gross & Pfister, 2004]. 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). Although relatively harmless, such benign condylomas are readily apparent and, as shown in the picture below of a promiscuous man who was still having sex at the time, can be quite shocking to look at.



