Human papillomavirus is an increasingly important cause of oropharyngeal cancer not only among white men, but also among women and nonwhite individuals, according to a retrospective cohort study published in JAMA Oncology.
HPV also causes a small proportion of nonoropharyngeal head and neck squamous cell cancer.
“Prevalence estimates of HPV in oropharyngeal squamous cell carcinomas (OPSCC) in the United States have been based on study populations consisting primarily of white men,” Gypsyamber D’Souza, PhD, associate professor in the division of cancer epidemiology at Johns Hopkins Bloomberg School of Public Health, and colleagues wrote. “Prevalence and trends of HPV–related OPSCC among women and nonwhites have not yet been well described. This multi-institutional study demonstrates a pronounced increase in the proportion of OPSCC cases caused by HPV in women and nonwhites over almost 2 decades. These data also address a knowledge gap regarding the role of HPV in nonoropharyngeal HNSCC.”
D’Souza and colleagues collected data from a stratified random sample of 863 patients (64% male; median age, 58 years; 36.7% white; 32.2% black; 19.6% Asian; 11.5% Hispanic) with newly diagnosed squamous cell carcinoma of the oral cavity (n = 253), larynx (n = 245), oropharynx (n = 240), or nasopharynx (n = 125). Patients were diagnosed between 1995 and 2012 at Johns Hopkins Hospital Sydney Kimmel Comprehensive Cancer Center and at University of California, San Francisco Helen Diller Family Comprehensive Cancer Center.
Researchers examined whether HPV caused a similar proportion of oropharyngeal cancers among women, Asians, Hispanics and blacks as it does among white men. Researchers also evaluated the role of HPV in nonoropharyngeal HNSCC.
Among 240 patients with OPSCC, 60% (n = 144) were p16 positive; 48% (n = 115) were HPV16 DNA in situ hybridization (ISH) positive; and 56% (n = 134) were positive for any oncogenic HPV type.
Data from 1995 to 2012 showed the proportion of p16–positive OPSCC increased significantly among women (29% to 77%; P = .005) and men (36% to 72%; P < .001), as well as among whites (39% to 86%; P < .001) and nonwhites (32% to 62%; P = .02). Researchers observed similar results for any oncogenic HPV OPSCC (P <.01 for all).
Among 623 nonoropharyngeal HNSCC, a higher proportion were p16 positive than ISH positive (10% vs. 5%; P = .001). Further, 42% of the p16–positive nonoropharyngeal HNSCC occurred in sites adjacent to the oropharynx.
The proportion of p16–positive and ISH–positive nonoropharyngeal HNSCC were similar by sex.
Over time, the proportion of nonoropharyngeal HNSCC that were p16 or ISH positive increased among whites (P = .04), but not among nonwhites.
Among OPSCC, p16 had 100% sensitivity, 91% specificity, 93% positive-predictive value and 100% negative-predictive value for ISH positivity. In nonoropharyngeal HNSCC, p16 had lower sensitivity (83%) and positive-predictive value (40%), but high specificity (94%) and negative-predictive value (99%) for ISH positivity.
Because researchers oversampled cases occurring in minorities and women for inclusion, they noted that overall and site-specific estimates of HPV prevalence may not be representative of cases at those anatomic sites.
These data address a knowledge gap regarding the role of HPV in nonoropharyngeal HNSCC, D’Souza and colleagues wrote.
“This is one of the first studies to explore the role of HPV in women, nonwhites and non-OPSCC in a large sample size in previously underreported groups with centralized testing and data spanning across two decades,” D’Souza and colleagues wrote.
A delayed increase in HPV–associated oropharyngeal incidence among women and nonwhites could be partly due to changes in behaviors and exposures that occurred earlier among white men than among nonwhites and women, Kristina R. Dahlstrom, PhD, and Erich M. Sturgis, MD, MPH, of the department of head and neck surgery at the University of Texas MD Anderson Cancer Center, and Karen S. Anderson, MD, of the Center for Personalized Diagnostics at Arizona State University, wrote in an accompanying editorial.
“The epidemiologic trends and the potential role of HPV at nonoropharyngeal head and neck cancer sites deserve further investigation,” Dahlstrom, Sturgis and Anderson wrote. “However, we should not lose focus on oropharyngeal carcinoma as the most dominant disease burden in the future, how to create a screening and early detection paradigm for oropharyngeal carcinoma, and how to define prognostic stratification to individualize oropharyngeal carcinoma care for improved and less-toxic outcomes.
“Finally, p16 expression is once again demonstrated to be an acceptable surrogate marker for HPV tumor status and prognosis for oropharyngeal carcinoma, but it cannot be used in isolation for cancers outside of the oropharynx,” they added. “As the incident of HPV–associated oropharyngeal carcinoma continues to increase, it is critical to distinguish between tumors that are HPV driven and those in which HPV has no impact; robust tumor testing, as well as serologic testing, will be vital to this goal.” – by Chuck Gormley
Disclosure: The researchers report no relevant financial disclosures. Anderson reports a paid consulting role and stock options with Provista Dx. Dahlstrom and Sturgis report no relevant financial disclosures.
Miriam N. Lango
There has recently been a dramatic increase in the incidence of oropharyngeal cancer caused by HPV, particularly in white men. In this study, Gypsyamber D’Souza, PhD, Carole Fakhry, MD, MPH, and their coauthors asked whether there has also been an increase in the incidence of this cancer in other groups, such as women and nonwhite individuals. Researchers also asked whether there has been an increase in cancer caused by HPV in other anatomic areas of the upper aerodigestive tract, such as the oral cavity and larynx. Finally, they asked what is the best method of identifying cancers caused by HPV, because there are different methods one could use.
In the study, 863 patients with squamous cell carcinoma were treated at Johns Hopkins Hospital and University of California, San Francisco. The analysis included patients with cancers of the oropharynx that are typically associated with HPV infection, as well as those with cancers of the oral cavity, larynx and nasopharynx.
The researchers found that over the study period, the cancers in female, Asian and Hispanic patients were more likely to test positive for p16, a commonly used marker for cancer caused by HPV. Females, Asians and Hispanics were as likely as white males to have an oropharyngeal cancer caused by HPV. This contrasts with black individuals with oropharyngeal cancer, who were far less likely to have a cancer caused by HPV.
The same pattern was observed when a different test for HPV was used — in situ hybridization testing for HPV.
The researchers also examined trends over time. They found that from 1995 through 2012, the prevalence of HPV–associated cancer increased dramatically in all groups tested, including black individuals, regardless of the testing method used. Over time, HPV has become a far more common cause of oropharyngeal cancer and, in most groups, is the most common cause of this cancer.
Some cancers in anatomic sites adjacent to the oropharynx, such as the larynx and nasopharynx, also tested positive for HPV. However, overall, cancers from these anatomic regions were far less likely to test positive using all testing methods and, particularly, to test positive using p16 staining, the test used most commonly to detect a cancer caused by HPV.
Overall, the role of HPV in cancers from anatomic sites other than the oropharynx needs further study.
The study is important because it shows that cancers in the oropharynx among women, Asian individuals and Hispanic individualss are as likely to be caused by HPV as those diagnosed in men. The proportion of oropharynx cancers caused by HPV has been increasing over time in all groups tested.
Although the prevalence of cancer caused by HPV is similar among groups, the incidence of cancer varies by group. For example, males are still more susceptible to HPV infection and oropharyngeal cancer caused by HPV. The reasons for differences in incidence are not well understood.