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Screening for oral HPV ‘would be challenging’ due to low throat cancer risk
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Lifetime risk for developing HPV-related oropharyngeal cancer appeared relatively low — 0.7% for men and 0.2% for women, according to study results.
Thus, despite increasing incidence, screening based on oncogenic HPV detection would present difficulties and is not recommended, according to the researchers.
“Our research shows that identifying those who have oral HPV infection does not predict their future risk [for] cancer well, and so screening based on detecting cancer-causing oral HPV infection would be challenging,” Carole Fakhry, MD, MPH, associate professor of oncology and otolaryngology-head and neck surgery at Johns Hopkins School of Medicine, said in a press release. “However, we are carrying out further research of oral HPV infection in young healthy men to explore this further.”
HPV causes approximately 70% of all oropharyngeal squamous cell cancers in the U.S., and it has been predicted that the incidence of oropharyngeal cancer will exceed cervical cancer by 2020.
Given this growing incidence and the frequency of sexual behaviors responsible for exposure to oral HPV, researchers seek to identify healthy individuals at highest risk for development of oropharyngeal squamous cell cancer.
“It would be useful to be able to identify healthy people who are most at risk [for] developing oropharyngeal cancer in order to inform potential screening strategies, if effective screening tests could be developed,” Gypsyamber D’Souza, PhD, MPH, MS, associate professor of epidemiology at Johns Hopkins University, said in a press release.
Fakhry, D’Souza and colleagues used the National Health and Nutrition Examination Survey to review oral HPV data from 13,089 adults aged 20 to 69 years to determine the frequency of HPV16, oncogenic HPV and HPV oropharyngeal squamous cell cancer among people with different risk factor profiles. Researchers used SEER data for information on oropharyngeal cancer cases and National Center for Health Statistics data to determine oropharyngeal cancer mortality.
To better understand subgroup risk, researchers reviewed the prevalence of oncogenic HPV and HPV16 after adjusting for multiple factors like sex, age, current smoking status and sexual behavior. The researchers combined groups with similar prevalence to create parsimonious risk stratification.
Prevalence of oncogenic HPV DNA in an oral rinse and gargle sample and incident oropharyngeal squamous cell cancer served as the primary outcomes.
Researchers detected oncogenic oral HPV DNA in 3.5% of adults, although the lifetime risk for oropharyngeal cancer — 37 per 10,000 individuals — remained low.
Prevalence of infection appeared higher among men than women (6% vs. 1.1%; P < .001). Oncogenic oral HPV prevalence increased with the number of lifetime oral sexual partners and smoking status.
Among men aged 50 to 59 years, 8.1% had oncogenic oral HPV infection and 2.1% had oral HPV16 infection. Still, only 0.7% of these men will ever develop oropharyngeal cancer in their lifetime, the researchers wrote.
Oncogenic HPV oral prevalence appeared highest — at 14.9% (95% CI, 11.4-19.1) — among men who smoked and had five or more lifetime oral sexual partners. Men who either smoked and had two to four sexual partners, or did not smoke and had at least five partners, had “medium risk,” with a prevalence of 7.3% (95% CI, 5.8-9.1).
Oncogenic oral HPV prevalence appeared low among individuals with one or fewer lifetime oral sexual partners — 0.7% for women and 1.7% for men — regardless of other risk factors.
“For most people these data should be very reassuring, as they show that their risk [for] oropharyngeal cancer is very low,” D’Souza said.
Mass screening for oral HPV infection is not recommended, D’Souza said in the release, because tests have more harms, such as false positives, than benefits.
“Currently available tests for the presence of oral HPV infections are not very predicative of oropharyngeal risk — most people who have an oral HPV infection will eventually clear it on their own,” D’Souza said.
Other studies are underway to develop tests that can be more predictive of HPV oropharyngeal cancer, Fakhry added.
“We have ongoing studies of strategies for using biomarkers to determine and stratify people’s oropharyngeal cancer risk,” Fakhry said. – by Melinda Stevens
Disclosures: The authors report no relevant financial disclosures.
Perspective
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Heather Osborn
HPV infections are increasingly common, reaching what some authors have termed epidemic proportions. These infections also are an increasingly significant cause of head and neck cancer, with roughly 70% of oropharyngeal cancers attributed to oncogenic HPV infections.
Recent media attention has increased patient anxiety about this disease process. Unfortunately, a reliable and cost-effective method of screening for oropharyngeal cancer has yet to be developed. This study by D’Souza and colleagues tackled the difficult topic of detection of oncogenic oral HPV infection as a screening method to identify patients at risk for oropharyngeal cancer. These authors examined a large series of 9,425 patients who had both oral HPV DNA test results, and available data regarding their lifetime number of oral sex partners. They also used data from SEER registries to determine the projected risk for oropharyngeal cancer in these populations. Overall, they found that oncogenic oral HPV is detected among only 3.5% of adults age 20 to 69 years, and that the lifetime risk for oropharyngeal cancer in this population is only 37 per 10,000. The researchers concluded that, due to the low prevalence of oral HPV infection, screening based upon oncogenic oral HPV infection will not be useful.
However, when they broke the study population down into subgroups, researchers were able to identify a high-risk subgroup of male patients: smokers who also have a lifetime history of five or more oral sex partners. This subgroup carried a much higher rate of oncogenic oral HPV infections, at 14.9%.
Although this analysis showed that oncogenic oral HPV DNA testing would be low yield in most populations in America, we should not undervalue the important work these authors did in identifying this high-risk subgroup. The utility of selective HPV DNA testing for only high-risk individuals has not been fully explored. In patients who meet the high-risk criteria, oncogenic oral HPV testing could help us to further understand their risk. Moreover, they could be surveilled with repeat HPV analysis, as in the HPV Infection in Males, or HIM, study, in which Pierce Campbell and colleagues followed patients over time with repeat assessments for oral HPV16 DNA to determine whether the infections persisted or cleared. Alternatively, positive patients could be targeted for periodic clinical and endoscopic examination.
Overall, this important study has identified a high-risk group, which allows clinicians to better stratify patients and also paves the way for further research on targeted screening of high-risk patients.
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