Invasive SCC of the penis is rare in the US, comprising 0.1% of all cancer diagnoses and deaths in men during 1998 to 2003. The average annual age-adjusted incidence of 0.81 per 100,000 is consistent with other Western countries, where incidence is below 1 per 100,000.1
There is considerable variation in the incidence of penile cancers. Reported incidence ranges from 0.04 per 100,000 in Jewish populations in Israel to 3 to 4 per 100,000 in Brazil and Uganda. High rates of penile cancer are also observed in India, Southeast Asia, Latin America, and Eastern and Southern Africa. The international variation in rates likely reflects differences in risk factors, which may also account for the disparities observed within the United States.
Although the overall burden of invasive penile cancer is limited in this country, there is considerable variation in its incidence and mortality. Hispanic men and those living in the South and in low socioeconomic areas were at substantially increased risk for penile SCC. The increased risk of penile SCC among Hispanics and the reduced risk among Asians-Pacific Islanders is consistent with 2 recent analyses and may reflect racial/ethnic differences in risk factors for penile carcinoma, including HPV exposure, circumcision status, and cigarette smoking.4,5
Genital HPV is a common, usually asymptomatic infection in men, with prevalence estimates from 1% to 73%.23
The excess risk of penile SCC among Hispanics may be at least partly attributed to circumcision status. Fewer Mexican Americans are circumcised than non-Hispanic whites,24
and uncircumcised men may be at increased risk of HPV infection25-29
and penile cancer.6,15,17,30
It is also possible that regional, socioeconomic, and racial/ethnic differences in penile cancer incidence reflect differences in sexual and other practices that influence exposure to HPV. Poverty, race, and ethnicity have been identified as risk factors for genital HPV infection in women.31
The younger age at diagnosis among blacks and Hispanics may be attributed to earlier exposure to HPV via early sexual contact.
The high rates of penile cancer among Hispanic men in the United States parallel the increased risk of cervical cancer among US Hispanics.32
High geographic correlation between the penis and cervical cancer incidence worldwide is evidence of a shared risk factor, namely, HPV infection.1
Nevertheless, although all cervical cancers are attributable to HPV, it is estimated that HPV is etiologically involved in approximately 40% of penile cancers. Multiple independent pathways for penis carcinogenesis, including those involving and not involving HPV, have been suggested.7
Previous studies have observed that HPV is detected less often in keratinizing and verrucous SCC than in other types such as basaloid and warty SCC.7,12
We were only able to examine 2 of the larger SCC subgroups: keratinizing and verrucous types. We observed some histologic differences by race and ethnicity. Asians/Pacific Islanders were at decreased of keratinizing SCC compared with whites, whereas Hispanic men were at increased risk of keratinizing SCC relative to non-Hispanics.
It is possible that penile cancers diagnosed at younger ages may have a poorer prognosis, which may account for the higher mortality observed in Hispanics and blacks. Alternatively, excess mortality of Hispanics and blacks and those living in the South and low SES regions may reflect disparities in health-care access.
Our results were consistent with other analyses demonstrating that the glans is the most common subsite of penis carcinoma.4,33
In situ tumors of the glans penis are clinically distinct from in situ cancers occurring on the shaft.34
Accordingly, invasive penile cancers occurring on the glans and shaft may have etiologic differences.
Penis amputation is standard therapy for invasive penile cancers.35
Local excision is generally used for more confined cancers. Advances in penile cancer treatment in the United States have emphasized more conservative surgical approaches, while also placing greater emphasis on lymphadenectomy to decrease the risk of metastasis and less emphasis on primary radiation treatment, given a high rate of recurrence.35
More aggressive treatment—including penile amputation and lymphadenectomy—was observed in advanced-stage disease, glans penis tumors, keratinizing SCCs, and moderately or poorly differentiated tumor grade. Younger men with penile SCCs were more likely to undergo lymphadenectomy and radiation. However, they were not more likely to undergo penile amputation, possibly reflecting concerns over preservation of sexual function. Glans penis tumors and keratinizing SCCs, which were more common among Hispanics, were more frequently treated through nonconservative means, possibly reflecting a more aggressive disease course.
There were several limitations to the present analysis. Population-based data from NPCR registries were not available before 1998; therefore, the present analysis was not able to examine national temporal trends in penile SCC incidence in the United States. Two recent studies of SEER data observed an overall decrease in penile cancer incidence over the past 3 decades.4,36
Subgroup analysis of histologic types was limited to the 2 largest groups: keratinizing and verrucous. We were not able to analyze other histologic types, such as basaloid and warty SCC. The ability to analyze differences by anatomic subsite was limited by missing data in a large proportion of cases. This may reflect gaps in reporting, which may be magnified for rarer cancers such as these. Measurements of SES were indirect and did not permit evaluation of the interaction of SES with geographic region, race, and ethnicity. The population coverage for treatment data, which was limited to SEER registries, was lower than that of incidence and mortality data, and this may have limited its representativeness. Treatment data were limited to first course rather than the complete treatment regimen.
The availability of prophylactic HPV vaccination for females may result in a decline in the incidence of HPV-associated penile malignancies in the United States in future years.37
Decreases in its incidence may also occur more directly should males become candidates for HPV immunization. Disparities in vaccine coverage within certain populations, including the medically underserved, however, may exacerbate the present disparities in penile SCC incidence and mortality. Further research is needed to better understand the epidemiology of penile cancer including the role of HPV and implications of prophylactic vaccination.