HPV OROPHARYNGEAL CANCER EPIDEMIC

There has been a rapid rise in the incidence of oropharyngeal cancer associated with human papillomavirus type 16 (HPV 16).

"We are clearly seeing an epidemic HPV-related head and neck cancer, and the numbers are rising dramatically," said Robert Haddad, MD, from the head and neck oncology program at the Dana-Farber Cancer Institute in Boston. Most of the increase in incidence has occurred in the past decade, he told Medscape Medical News in an interview.

"In my clinic, I am seeing 1 or 2 patients per week with this entity. These are typically young patients, in their 40s and early 50s, they are nonsmokers and nondrinkers, and they are presenting with stage IV locally advanced oropharynx cancer." This is the area at the base of the tongue and around the tonsils, where the HPV cancer usually starts, he explained.

"There is clearly a rise in this entity...and we don't necessarily know why," he said. It has been attributed to the increase in sexual behaviors such as oral sex with multiple partners as a result of the "sexual revolution" in the 1960s, but this has been questioned. Studies investigating the association between oral sex and oral HPV infection have had inconsistent results. Dr. Haddad believes that changes in sexual behavior are only part of the story; "there is a lot more that we don't know yet," he explained.

A new study of oral HPV infection in men, published online July 2 in the Lancet, has found no clear link with oral sex. However, it looked at oral HPV infection, not HPV oropharyngeal cancer, Dr. Haddad noted. He stressed that HPV 16 infection does lead to oropharyngeal cancer, "but it is very important to note that this risk is extremely small," he added.

The study authors, led by Aimée Kreimer, PhD, from the National Cancer Institute in Bethesda, Maryland, found "no significant association between any measure of oral sexual behavior and acquisition of oncogenic HPV after adjustment for potential cofounders."

Their study involved 1626 men 18 to 73 years of age from Brazil, Mexico, and the United States. Median follow-up was 12.7 months.

During the first 12 months of follow-up, 4.4% of men acquired an incident oral HPV infection, 1.7% acquired an oral oncogenic HPV infection (HPV type 16, 18, 39, or 59), and 0.6% acquired an oral HPV 16 infection.

Acquisition of an oral oncogenic HPV infection was significantly associated with smoking and not being married or cohabiting. This was similar across countries, age groups, and reported sexual behaviors.

The median duration of infection was 6.9 months for any HPV infection, 6.3 months for oncogenic HPV, and 7.3 months for HPV 16.

"Newly acquired oral oncogenic HPV infections in healthy men were rare and most were cleared with 1 year," the authors report.

Dr. Haddad noted that in this study, HPV infection was measured from a sample of saliva (obtained using an oral rinse and gargle), which could have underestimated the true incidence of infection.

The association between HPV 16 oral infections and smoking is interesting because most patients with HPV oropharyngeal cancer are nonsmokers, said Dr. Haddad. However, in this study, the risk of having an oral HPV 16 infection was 3-fold higher in current smokers and 2-fold higher in former smokers, he noted.

"Tobacco exposure induces proinflammatory and immunosuppressive effects, which might increase the likelihood of HPV infection and persistence, particularly at the oral cavity where tobacco carcinogens have direct contact with the oral epithelium," Dr. Kreimer and colleagues note.

There was also a significant association between martial status and the risk of acquiring any oncogenic HPV infection. Men who were married or cohabiting were at significantly lower risk than men who were single, divorced, separated, or widowed.

"Marital status seems to be more predictive of oral HPV acquisition than does lifetime number of sexual partners," the authors report. However, these findings are in contrast with those from previous studies, which found an association with the number of lifetime and recent partners, they note.

"Our findings show that acquisition of an oral oncogenic HPV infection in healthy men is a rare event (2.5 per 1000 person-months) compared with genital (22.2 per 1000 person-months) and, to a lesser extent, anal (3.7 per 1000 person-months) HPV infection," the authors write.

"Most of our knowledge of HPV epidemiology relates to the cervix, where HPV occurs shortly after sexual debut, most infections clear within 1–2 years, and infections at older ages are uncommon," they write.

"Our findings suggest different epidemiological characteristics for oral HPV infection in men," they add. The increased prevalence of oral HPV at older ages might be caused by the increased duration of infection at older ages, rather than increased incidence, they note.

Lancet. Published online July 2, 2013. Abstract