Penile cancer risk factors

Researchers find high prevalence of human papillomavirus in men with penile cancer
Dr. Janet Daling
Dr. Janet Daling and colleague discuss their long-term study that related human papillomavirus (HPV) with other risk factors for penile cancer. Photo by Todd McNaught

Infection with a virus known for its link to cervical cancer is also a key risk factor for penile cancer, according to a long-term study of more than 800 men in western Washington.

The study, led by Hutchinson Center and University of Washington researchers, found that in addition to the human papillomavirus (HPV), lack of circumcision, cigarette smoking and phimosis (inability to retract the foreskin) also played key roles in the development of invasive penile cancer. Few previous studies have related HPV infection with other risk factors.

The results, published in the April issue of the International Journal of Cancer, revealed that HPV was detected in almost 80 percent of the tumors. More than 69 percent of the cases were HPV-16 positive, a high-risk form of the sexually transmitted disease.

Dr. Janet Daling, lead author of the paper and a researcher in the Public Health Sciences Division, said the high prevalence of HPV challenged previous assumptions. "In the past, people have not thought that HPV played as big a role as we found," she said.

Despite the increased risk of penile cancer for uncircumcised males, Daling cautioned against circumcision as a means of protection. "The big controversy with this cancer is what role circumcision plays," she said. "This paper clearly shows that circumcision had no relationship to infection with HPV. Being circumcised to prevent penile cancer is ridiculous because it's so rare in our country."

Circumcision eliminates phimosis, a condition present in about 35 percent of the study participants with invasive cancer who were not circumcised as children. Penile tears, rashes and injuries — often caused by the condition — were associated with an increased risk of the disease. However, when the researchers restricted their analysis to men who did not have phimosis, the risk of invasive cancer associated with not having been circumcised was not elevated.

Penile cancer affects about one in 100,000 men in North America and Europe each year. It is so uncommon in the United States that urologists may only see two or three cases in their entire careers.

In the rest of the world, the situation is different and represents an important health problem. Penile cancer represents 20 percent of all cancers diagnosed in men living in Asia, Africa and South America. Researchers believe that unsanitary conditions in these countries may contribute to the higher rates of penile cancer, as they make personal hygiene more difficult. Without frequent cleaning, oily secretions called smegma can accumulate under the foreskin and cause inflammation of the penis.

The National Cancer Institute-funded study included 137 men with in situ (non-invasive) or invasive penile cancer diagnosed between 1979 and 1998 as well as 671 unaffected men for comparison.

Both groups of men were interviewed in person about prior health conditions, age at circumcision, hygienic practices, sexual and other behaviors, and they provided blood samples. For those diagnosed with penile cancer, tissue specimens were obtained for the majority of the cases.

Current cigarette smoking was associated with more than a four-fold risk of invasive penile cancer. Smoking has been implicated in the development of all anogential cancers. "We don't know what role it plays for sure, but some studies have shown smoking may inhibit programmed cell death, so potentially cancerous cells may accumulate in smokers," Daling said.

HPV is an umbrella term for more than 100 different strains of the virus, about 30 of which are sexually transmitted. Some of these viruses are high-risk types and may cause abnormal Pap tests for women, but there are no tests for men. Most people who become infected with HPV do not have any symptoms. HPV-vaccine clinical trials are underway, and early results are promising.

Co-authors included Dr. Margaret Madeleine, Dr. Steve Schwartz, Dr. Lisa Johnson, Katherine Shera, Michelle Wurscher, Dr. Joseph Carter, Dr. Peggy Porter, Dr. Denise Galloway and the late Dr. James McDougall, of the Hutchinson Center; and Dr. John Krieger, UW.

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