Summary Human papillomavirus (HPV) is etiologically responsible for a distinct subset of head and neck squamous cell cancers (HNSCCs). HPV-positive HNSCCs (HPV-HNSCCs) most commonly arise from the ...oropharynx and are responsible for the increasing incidence of oropharyngeal SCC (OSCC) in the United States (US) and abroad. HPV-positive OSCC (HPV-OSCC) has a unique demographic and risk factor profile and tumor biology. HPV-OSCC patients tend to be white, younger, and have a higher cumulative exposure to sexual behaviors as compared with HPV-negative OSCC patients. HPV-positive tumor status also significantly improves survival, and is indeed the single strongest prognostic factor for OSCC. The mechanisms that underlie the improved prognosis conferred by HPV-positive disease are unknown. The purpose of this review is to describe the clinical impact of HPV status in HNSCC, particularly in OSCC, both in terms of the unique clinic-demographic profile and prognostic implications.
Human papillomavirus (HPV) is now established as the principal cause of an increase in incidence of a subset of head and neck squamous cell cancers (HNCs) in numerous geographic regions around the ...world. Further study of the epidemiology of HPV-positive HNC will be critical to the development and implementation of public health interventions to reverse these global incidence trends. Here, recent data are reviewed to provide insight into several topics, including incidence trends and projections for HPV-positive HNC; the worldwide HPV-attributable fraction; sex disparities in cancer risk; the epidemiology of oral HPV infection; the latency period between infection and cancer; the potential impact of prophylactic HPV vaccination; and prospects for secondary prevention through screening for oral HPV infection or seroreactivity to viral antigens. The identification of a single necessary cause for any cancer provides a rare and perhaps extraordinary opportunity for cancer prevention.
Human papillomavirus (HPV) is now recognized to play a role in the pathogenesis of a subset of head and neck squamous cell carcinomas (HNSCCs), particularly those that arise from the lingual and ...palatine tonsils within the oropharynx. High-risk HPV16 is identified in the overwhelming majority of HPV-positive tumors, which have molecular-genetic alterations indicative of viral oncogene function. Measures of HPV exposure, including sexual behaviors, seropositivity to HPV16, and oral, high-risk HPV infection, are associated with increased risk for oropharyngeal cancer. HPV infection may be altering the demographics of HNSCC patients, as these patients tend to be younger, nonsmokers, and nondrinkers. There is sufficient evidence to conclude that a diagnosis of HPV-positive HNSCC has significant prognostic implications; these patients have at least half the risk of death from HNSCC when compared with the HPV-negative patient. The HPV etiology of these tumors may have future clinical implications for the diagnosis, therapy, screening, and prevention of HNSCC.
This study explores whether gender, age and race differences in oral sexual behavior account for the demographic distribution of oral human papillomavirus infection (HPV) and HPV-positive ...oropharyngeal cancer (HPV-OSCC).
This analysis included 2,116 men and 2,140 women from NHANES (2009-10) who answered a behavioral questionnaire and provided an oral-rinse sample for HPV detection. Weighted prevalence estimates and prevalence ratios (PR) were calculated for sexual behaviors and oral HPV infection by gender, age-cohort (20-29, 30-44, 45-59, 60-69), and race, and contrasted with incidence rate ratios (IRR) of OSCC from SEER 2009. Multivariate logistic regression was used to evaluate predictors of oral sexual behavior and oral HPV16 infection.
Differences in oral sexual behavior were observed by gender, age-cohort and race. Most men (85.4%) and women (83.2%) had ever performed oral sex, but men had more lifetime oral and vaginal sexual partners and higher oral HPV16 prevalence than women (each p<0.001). 60-69 year olds (yo) were less likely than 45-59 or 30-44 (yo) to have performed oral sex (72.7%, 84.8%, and 90.3%, p<0.001), although oral HPV16 prevalence was similar. Prevalence ratios (PR) of ever oral sex in men vs. women (PR = 1.03), and 45-59 vs. 30-44 year-old men (PR = 0.96) were modest relative to ratios for oral HPV16 infection (PRs = 1.3-6.8) and OSCC (IRR = 4.7-8.1). In multivariate analysis, gender, age-cohort, and race were significant predictors of oral sexual behavior. Oral sexual behavior was the primary predictor of oral HPV16 infection; once this behavior was adjusted for, age-cohort and race were no longer associated with oral HPV16.
There are differences in oral sexual behaviors when considering gender, age-cohort and race which explain observed epidemiologic differences in oral HPV16 infection across these groups.
Objective
To summarize the epidemiology of human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinomas (OSCC).
Data Sources
Articles in the English language referenced in MEDLINE/PubMed ...from the year 2000 onward.
Review Methods
Relevant articles pertaining to the epidemiology of HPV‐related OSCC were selected for review, with a particular preference for articles from 2008 onward.
Results
The incidence of HPV‐related OSCC continues to increase in North America and Western Europe, with up to 70% of new oropharyngeal cancer cases being attributed to HPV, whereas data from the developing world remain lacking. There is evidence to support distinct risk factors for HPV‐related OSCC as compared with HPV‐unrelated OSCC. The long‐term natural history of HPV infections remains unknown. HPV‐related OSCC are associated with an improved prognosis both at the time of primary diagnosis and disease progression. There is preliminary evidence to show that HPV vaccination initiatives are effective in preventing HPV cervical infections, although data related to oral HPV infections are lacking.
Conclusion
The epidemiology of HPV‐related OSCC is evolving. Further efforts are needed to characterize the natural history of oral HPV infection and its relationship with the eventual development of HPV‐associated OSCC to develop effective tools for secondary prevention.
Level of Evidence
NA Laryngoscope, 126:894–900, 2016
Human papillomavirus positive oropharyngeal cancer (HPV-positive OPC) is a distinct subtype of head and neck carcinoma (HNC) distinguished from HPV-negative HNC by its risk factor profile, clinical ...behavior, and molecular biology. Compared to HPV-negative HNC, HPV-positive OPC exhibits significantly better prognosis and an enhanced response to treatment. Recognition of the survival benefit of HPV-positive tumors has led to therapeutic de-intensification strategies aiming to mitigate treatment-related toxicities while maintaining high response rates. In this review, we summarize key aspects of oral HPV infection and the molecular mechanisms of HPV-related carcinogenesis. We review the clinical and molecular characteristics of HPV-positive OPC that contribute to its improved prognosis compared to HPV-negative HNC. We also discuss current and emerging treatment strategies, emphasizing potential mechanisms of treatment sensitivity and the role of therapeutic de-intensification in HPV-positive OPC. Lastly, we examine literature on the management and prognosis of recurrent/metastatic HPV-positive OPC with a focus on the role of salvage surgery in its management.
Risk of cancer progression is reduced for patients with human papillomavirus (HPV) -positive oropharynx cancer (OPC) relative to HPV-negative OPC, but it is unknown whether risk of death after ...progression is similarly reduced.
Patients with stage III-IV OPC enrolled onto Radiation Therapy Oncology Group trials 0129 or RTOG 0522 who had known tumor p16 status plus local, regional, and/or distant progression after receiving platinum-based chemoradiotherapy were eligible for a retrospective analysis of the association between tumor p16 status and overall survival (OS) after disease progression. Rates were estimated by Kaplan-Meier method and compared by log-rank; hazard ratios (HRs) were estimated by Cox models. Tests and models were stratified by treatment protocol.
A total of 181 patients with p16-positive (n = 105) or p16-negative (n = 76) OPC were included in the analysis. Patterns of failure and median time to progression (8.2 v 7.3 months; P = .67) were similar for patients with p16-positive and p16-negative tumors. After a median follow-up period of 4.0 years after disease progression, patients with p16-positive OPC had significantly improved survival rates compared with p16-negative patients (2-year OS, 54.6% v 27.6%; median, 2.6 v 0.8 years; P < .001). p16-positive tumor status (HR, 0.48; 95% CI, 0.31 to 0.74) and receipt of salvage surgery (HR, 0.48; 95% CI; 0.27 to 0.84) reduced risk of death after disease progression whereas distant versus locoregional progression (HR, 1.99; 95% CI, 1.28 to 3.09) increased risk, after adjustment for tumor stage and cigarette pack-years at enrollment.
Tumor HPV status is a strong and independent predictor of OS after disease progression and should be a stratification factor for clinical trials for patients with recurrent or metastatic OPC.
Highlights • While tobacco related head and neck cancers are decreasing, HPV-related ones are increasing. • HPV (+) cancer patients are typically younger (40 s–50 s), white, and have not used ...tobacco. • HPV (+) cancer typically presents in the oropharynx and responds better to treatment. • P16 stain is a reliable test for HPV recommended in all oropharyngeal cancers. • HPV infection risk may be lowered with vaccination prior to becoming sexually active.
•Among people with HNSCC, oral HPV detection has good specificity (92%) and moderate sensitivity (72%) for HPV-positive HNSCC.•The utility of oral HPV detection to screen for HNSCC among healthy ...populations is probably limited, as there would be many false-positives.
The incidence of HPV-related head and neck squamous cell carcinoma (HPV-HNSCC) is increasing. Oral samples are easy and non-invasive to collect, but the diagnostic accuracy of oral HPV detection methods for classifying HPV-positive HNSCC tumors has not been well explored.
In a systematic review, we identified eight studies of HNSCC patients meeting our eligibility criteria of having: (1) HPV detection in oral rinse or oral swab samples, (2) tumor HPV or p16 testing, (3) a publication date within the last 10 years (January 2007–May 2017, as laboratory methods change), and (4) at least 15 HNSCC cases. Data were abstracted from each study and a meta-analysis performed to calculate sensitivity and specificity.
Eight articles meeting inclusion criteria were identified. Among people diagnosed with HNSCC, oral HPV detection has good specificity (92%, 95% CI = 82–97%) and moderate sensitivity (72%, 95% CI = 45–89%) for HPV-positive HNSCC tumor. Results were similar when restricted to studies with only oropharyngeal cancer cases, with oral rinse samples, or testing for HPV16 DNA (instead of any oncogenic HPV) in the oral samples.
Among those who already have HNSCC, oral HPV detection has few false-positives but may miss one-half to one-quarter of HPV-related cases (false-negatives). Given these findings in cancer patients, the utility of oral rinses and swabs as screening tests for HPV-HNSCC among healthy populations is probably limited.
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