White men older than age 65 will have the greatest burden of oropharyngeal cancer by the year 2030, according to Maura L. Gillison, MD, PhD, Professor and Endowed Chair at MD Anderson Cancer Center in Houston. But there is some good news, she said at the 2019 Winship Cancer Institute of Emory University Updates in the Management of Head and Neck Cancer Symposium.1 The human papillomavirus (HPV) vaccine has had a significant impact on reducing the HPV infections that can lead to head and neck cancers and reduced vaccine-type oral HPV infections in men in the United States by 37% over the span of 8 years.2
Maura L. Gillison, MD, PhD
The global burden of squamous cell head and neck carcinomas caused by HPV is estimated to be about 37,200 cases annually, 29,000 of which are classified as oropharyngeal cancers. HPV-positive oral cavity cancers account for about 4,400 cases yearly, and laryngeal cancers account for 3,800.3 “But I think [the burden of HPV-positive oropharyngeal cancers] is a gross underestimate, because we’re pretty close to that number in the United States alone,” she noted.
The Centers for Disease Control and Prevention issued a press release in 2015 stating that for the first time, oropharyngeal cancers have surpassed cervical cancer as the main HPV-related malignancy in the U.S. population. Meanwhile, other HPV-associated cancers are still on the rise, despite the development of the HPV vaccine. As of 2015, a total of 33,737 cancer cases were attributed to HPV infection, compared with 26,000 in 1999.4
When the incidence rates for oropharyngeal cancer in the United States are stratified by sex, it becomes clear that they are increasing most dramatically for white men.5 Far more moderate but still significant increases in incidence rates have been observed among white women.
Younger vs Older Men
According to Dr. Gillison and her collaborator, Anil Chaturvedi, PhD, of the National Cancer Institute (NCI), the dramatic increase in the rates of oropharyngeal cancer among white men is a result of a strong birth cohort effect, most likely driven by changes in sexual behavior. “It’s been accelerating 5% per year since 1945, but more recently, the rate at which it’s accelerating is moderating among white men,” she said. “We hypothesize that this moderation tracks to the birth cohort that was most affected by the HIV epidemic, which profoundly affected our sexual behavior in the United States.”
When the incidence data were stratified annually by birth cohort, it was observed that white men born after 1935 or 1940, who were in their teens and early 20s during the sexual revolution of the 1960s, “led the wave,” she added. In the 1990s, at the start of the rapid rise in oropharyngeal cancer rates, this population cohort was in their 40s.
“When we first described the rise in oropharyngeal cancer rates, it was rising most dramatically among young men in the United States. But these birth cohorts are 20 years older now,” she explained. “So, moving forward, instead of this being predominately a disease of young men, the bulk of it is going to be in those older than age 65.”
Compared with a younger, otherwise healthy population, treating an older population with more significant comorbidities requires a different approach to de-intensification. “The question now is altered to how to enhance and maintain survival outcomes while dealing with potential complications given comorbidities and age,” noted Dr. Gillison.
By the year 2030, it is anticipated that the burden will increase by another 50%, from 20,000 to 30,000 new diagnoses of HPV-positive oropharyngeal cancer per year, the vast majority occurring among white men.5 “Our clinics are struggling to keep up with this burden,” she said.
‘Vaccine Could Be 100% Effective’
To date, no trial has evaluated the effectiveness of vaccines against oral HPV infections that can lead to cancer—particularly among men. In collaboration with the Centers for Disease Control and Prevention and the NCI, Dr. Gillison conducted a statistical sampling of the U.S. population in which they tested for oral HPV infection and evaluated the associations with demographics and behaviors.
Their first report revealed that men in the sampling were five times more likely to have HPV16 infection, elucidating one of the reasons why men are at higher risk of this disease.6,7 The researchers went on to ask men and women between the ages of 18 and 33 whether or not they received the HPV vaccine; they observed a significant reduction in HPV16/18/6/11 prevalence in vaccinated individuals. Among men who reported receiving at least one vaccine dose, no HPV16 or 18 infections were detected.8
“What we saw was that individuals who had received the vaccine were far less likely to have a prevalent vaccine type infection, but there wasn’t any difference in the nonvaccine types,” she reported. “So, we estimated that the vaccine could be as high as 100% effective.”
What About Herd Immunity?
Since the approval of the HPV vaccine, the number of vaccinated individuals has risen significantly. From 2009 to 2016, the number of vaccinated men between the ages of 18 and 26 rose from 0% to about 19%; among women, it rose from about 24% to about 50%.2
Among men who were never vaccinated, the researchers observed no differences in nonvaccine-type HPV infections with regard to prevalence, but they saw a 37% decline in vaccine-type HPV infections between 2009 and 2016—a trend that was statistically significant. No significant changes were observed among women, because the prevalence in women is so much lower than in men, and any changes in data are difficult to see, she noted.
“As of 2016, it looks as though the HPV vaccine reduced HPV16 and 18 infections by 37% in men up to the age of 59, which is good news,” stated Dr. Gillison. “So, let’s continue to advocate for HPV vaccination for the prevention of genital disease; the potential benefit in the population is that infections leading to head neck cancers may also be prevented.” ■
DISCLOSURE: Dr. Gillison is a consultant/advisor for Bristol-Myers Squibb, Merck, EMD Serono, Roche, Genocea Biosciences, and BioMimetix; and has received institutional research funding from Bristol-Myers Squibb and Genocea Biosciences.
REFERENCES
1. Gillison M: HPV. 2019 Winship Cancer Institute of Emory University Updates in the Management of Head and Neck Cancer Symposium. Presented April 27, 2019.
2. Chaturvedi AK, Gillison M: JAMA 322:977-979, 2019.
3. de Martel C, Plummer M, Vignat J, et al: Int J Cancer 141:664-670, 2017.
4. National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology & End Results (SEER): NPCR and SEER Incidence—U.S. Cancer Statistics Public Use Database Data Standards and Data Dictionary. November 2017 Submission, Diagnosis Years 2001–2015. Available at www.cdc.gov/cancer/uscs/public-use/pdf/npcr-seer-public-use-database-data-dictionary-2001-2015-508.pdf. Accessed May 20, 2019.
5. Tota JE, Best AF, Zumsteg ZS, et al: J Clin Oncol 37:1538-1546, 2019.
6. Gillison ML, Broutian T, Pickard RK, et al: JAMA 307:693-703, 2012.
7. Chaturvedi AK, Graubard BI, Broutian T, et al: Cancer Res 75:2468-2477, 2015.
8. Chaturvedi AK, Graubard BI, Broutian T, et al: J Clin Oncol 36:262-267, 2018.
