Penile cancer: Importance of circumcision, human papillomavirus and smoking in in situ and invasive disease

Abstract

Few population-based case-control studies have assessed etiologic factors for penile cancer. Past infection with high-risk human papillomavirus (HPV) is a known risk factor for penile cancer; however, few previous studies have related the HPV DNA status of the tumor to potential demographic and behavioral risk factors for the disease or evaluated whether in situ and invasive penile cancer share risk factors. Little information is available on the role and timing of circumcision in the etiology of penile cancer. We conducted a population-based case-control study in western Washington state that included 137 men diagnosed with in situ (n 5 75) or invasive (n 5 62) penile cancer between January 1, 1979, and December 31, 1998, and 671 control men identified through random digit dialing. Cases and controls were interviewed in person and provided peripheral blood samples. Case and control blood samples were tested for antibodies to HPV16 and HSV-2, and tumor specimens from cases were tested for HPV DNA. Men not circumcised during childhood were at increased risk of invasive (OR 5 2.3, 95% CI 1.3-4.1) but not in situ (OR 5 1.1, 95% CI 0.6-1.8) penile cancer. Approximately 35% of men with penile cancer who had not been circumcised in childhood reported a history of phimosis compared to 7.6% of controls (OR 5 7.4, 95% CI 3.7-15.0). Penile conditions such as tear, rash and injury were associated with increased risk of disease. Among men not circumcised in childhood, phimosis was strongly associated with development of invasive penile cancer (OR 5 11.4, 95% CI 5.0-25.9). When we restricted our analysis to men who did not have phimosis, the risk of invasive penile cancer associated with not having been circumcised in childhood was not elevated (OR 5 0.5, 95% CI 0.1-2.5). Cigarette smoking was associated with a 4.5-fold risk (95% CI 2.0-10.1) of invasive penile cancer. HPV DNA was detected in 79.8% of tumor specimens, and 69.1% of tumors were HPV16-positive. The proportion of HPV DNA-positive tumors did not vary by any risk factors evaluated. Many risk factors were common for both in situ and invasive disease. However, 3 factors that did not increase the risk for in situ cancer proved significant risk factors for invasive penile cancer: lack of circumcision during childhood, phimosis and cigarette smoking. The high percentage of HPV DNA-positive tumors in our study is consistent with a strong association between HPV infection and the development of penile cancer regardless of circumcision status. Circumcision in early childhood may help prevent penile cancer by eliminating phimosis, a significant risk factor for the disease. ' 2005 Wiley-Liss, Inc.

Profile of Patients with Penile Neoplasms Who Have Undergone Penectomy

“…These factors have also been identified in other studies [27][28][29][30], among which people cited as main risk factors the presence of phimosis, low socioeconomic conditions, large number of sexual partners, history of sexually transmitted disease, especially HPV, poor hygiene, smoking, inflammation, and presence of sores or ulcerations in the penis.…”

Male Circumcision: Implications for Women as Sexual Partners and Parents

“…Systematic reviews show that circumcised men are at significantly lower risk of syphilis and chancroid. 8,9 Circumcised men in the United States are also at significantly lower risk of invasive penile cancer, [10][11][12][13] and a lower risk of cervical cancer in partners of circumcised men has also been reported. 14 This may be due to decreased human papillomavirus infection, which causes ano-genital and cervical cancer.…”

Human papillomavirus genotypes and HPV16 variants in penile carcinoma

“…11 The prevalence of HPV-related high-grade penile intraepithelial neoplasia, however, is very low suggesting that penile tissue is less prone to maintain persistent infection and to undergo neoplastic transformation. As for the cervical cancer pathogenesis, several additional risk factors have been reported, in conjunction with HPV infection, for the development of invasive penile cancer: (i) exogenous cofactors (lack of circumcision in childhood, phimosis, smoking, trauma), 12,13 (ii) host cofactors (genetic factors, immune response) 14,15 and (iii) viral cofactors (infection by specific types, viral load, viral integration status).The frequency of HPV DNA in penile carcinomas greatly vary depending on the tumor histology, the type of analyzed tissue (fresh frozen biopsies versus paraffin-embedded archival samples), virus detection methods and geographical origin. [15][16][17][18][19][20][21][22][23][24][25][26][27] HPV16 is the most prevalent type in penile carcinoma and cervical carcinoma worldwide, with exception of the study by Senba et al, which found HPV18 in 55.4% of the tumors from northern Thailand.…”