HPV Throat Cancer in Men Increasing -- Link to Oral Sex?

Roxanne Nelson, BSN, RN

February 29, 2016

Human papillomavirus (HPV) now causes the majority of oropharyngeal cancers in the United States, and the incidence is rising, especially among men.

Men are twice as likely as women to develop oropharyngeal cancers that are linked to HPV, according to new data presented at the recent annual meeting of the American Association for the Advancement of Science (AAAS).

"Men are not only more likely to become infected with oral HPV infection than women, but our research also showed that once you become infected, men are less likely to clear these infections than women, further contributing to their cancer risk," said Gypsyamber D'Souza, PhD, an associate professor in the Viral Oncology and Cancer Prevention and Control Program at the Johns Hopkins Bloomberg School of Public Health, in Baltimore, Maryland, who presented the research.

Their recent data showed that men were 37% less likely than women (adjusted hazard ratio [HR] = 0.63) to clear an oral HPV infection.

Oral sex is the main risk factor for oral HPV infection, and previous research has found that performing oral sex is more common in younger generations than in older age groups. Among the younger generation, there is also a tendency to have more partners and to engage in sexual behaviors at a younger age.

"These differences in sexual behavior across age cohorts explain the differences that we see in oral HPV prevalence and in HPV-related oropharyngeal cancer across the generations and why the rate of this cancer is increasing," Dr D'Souza said.

"But differences in sexual behavior do not explain the differences that we see between men and women in oral HPV infection and HPV-related cancer," she added.

Dr D'Souza's talk was partly drawn from a recent study that she coauthored, which was published online February 10 in the Journal of Infectious Diseases.

Oropharyngeal squamous cell carcinoma (OPSCC) is generally caused by HPV type 16 (HPV16), Dr D'Souza and her colleagues note.

The higher risk for OPSCC among men in the United States is partially explained by a fivefold higher prevalence of oral HPV16, but the factors contributing to the difference in prevalence seen among the sexes are unclear.

Sex Paradox

To better understand the differences in prevalence seen among the sexes, Dr D'Souza and colleagues conducted a prospective study of oral HPV infection among 409 young adult men and women aged 18 to 25 years. The participants were enrolled in the Study of Papillomavirus in Teens and Twenties (SPITT); they were followed every 3 months for 18 months.

For those with persistent infection at their 18-month visit, follow-up was extended to 30 months.

Men were more likely to report >10 lifetime vaginal sexual partners (51% vs 32%), >1 recent vaginal sexual partners (50% vs 36%), and >1 recent oral sexual partners (28% vs. 22%) (P < .05 for all).

Oral HPV prevalence and incidence were higher in the male participants than in the women. At baseline, 68 prevalent, type-specific oral HPV infections were detected among 44 (11%) participants (15.4% in men vs 5.6% in women; P = .001).

The incidence of HPV16 infection was higher among men than women (2.5 vs 0.7 per 1000 person-months; P = .08), as was the incidence of any oncogenic HPV infections (15.5 vs 8.9 per 1000 person-months; P = .04) Most notable were the interactions between sexes, oral sexual behavior, and risk for incident oral HPV infection, the authors note. The recent performance of oral sex significantly increased risk for oral HPV infection in men but not women (HR, 3.15 vs 0.66; P-interaction, [PI] = 0.01).

The risk for infection increased significantly with the number of recent oral sexual partners among men but not women (PI = .052).

Conversely, the risk significantly declined with higher lifetime number of vaginal sexual partners among women but not men (PI = .037).

The reason for this paradox may be that when women are first exposed to HPV vaginally, they mount an immune response that prevents them from developing an oral HPV infection, Dr D'Souza explained.

Weaker Immune Response?

But men do not seem to exhibit an equally robust immune response to HPV.

Viral clearance was significantly longer in men, the authors note. The median time to clearance for both men and women overall was 3.7 months, with 24% of infections persisting to 12 months.

However, there was a difference between the sexes ― the median time to clearance was 5.3 months for men vs 3.0 months for women (P < .001).

When looking only at clearance for HPV16 infections, the median time continued to remain higher among men than women (7.5 vs 3.5 months; P = .34) but was not statistically significant.

"As to clinical significance of findings at this time with regard to interactions between sexual behavior, gender, and oral HPV infection, there are no direct clinical implications," commented Maura Gillison, MD, PhD, from the Ohio State University Comprehensive Cancer Center, in Columbus. Dr Gillison is the senior author of the study.

"Instead, these findings may help to explain gender differences in ongoing incidence trends for these cancers," Dr Gillison told Medscape Medical News. "The data allow us to generate a hypothesis that seroconversion among women in response to natural infection confers subsequent protection against new infections.

"This has been shown among women for cervical infection," Dr Gillison added. However, this hypothesis has yet to be proven with regard to oral HPV infections in men or women.

In a study published last month, Dr Gillison and colleagues reported that the detection of oral HPV16 in the mouth is associated with a 22-fold increased risk for incident oropharyngeal cancer.

Implications for the Future

These data are very interesting, commented A. Ross Kerr, DDS, MSD, clinical associate professor of oral and maxillofacial pathology, radiology, and medicine at New York University, in New York City.

 
It could be that women may develop some sort of immunity. Dr A. Ross Kerr
 

"It could be that women may develop some sort of immunity, because they don't seem to pick it up as readily from men or other women when performing oral sex," Dr Kerr said in an interview.

Dr Kerr also pointed out that the incidence of non-HPV-related oropharyngeal cancers has also been found to be higher in men than women.

"It was about a 3-to-1 ratio, and behaviors like smoking were correlating with these rates," he said. "We feel that certain behaviors were playing a role, as well as other issues, such as socioeconomic status, which plays into the stage of the cancer at diagnosis, which in turn affects survival."

During visual examination of the soft tissues of the mouth, dentists can play a role in detecting oral cancers, although oropharyngeal cancers are more difficult to see during a routine examination, he point out.

"But once we understand the natural history of the disease, I think dental offices could play a role in HPV screening," Dr Kerr said, "although right now, we are not quite ready for that."

Dentists may understandably be uncomfortable asking questions about sexual behaviors, so one possibility could be to have the patient fill out a questionnaire. On the basis of the responses, an HPV test could be administered. Follow-up would depend on the results.

"But we're not there yet," he emphasized. "Once we better understand the natural history of HPV, we can devise strategies for intercepting the disease at earlier stages."

The authors note that their findings underscore the need for HPV vaccination among boys as well as girls, and Dr Kerr said he concurs.

The study was supported in part by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp and by the Oral Cancer Foundation. Dr D'Souza received research support from Merck Sharp & Dohme Corp. The other authors of the article have disclosed no relevant financial relationships.

J Infect Dis. Published online February 10, 2016. Abstract

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