Dataset Information

Survival outcomes by high-risk human papillomavirus status in nonoropharyngeal head and neck squamous cell carcinomas: A propensity-scored analysis of the National Cancer Data Base.

ABSTRACT: BACKGROUND:The prognostic relevance of human papillomavirus (HPV) status in patients with nonoropharyngeal (OPX) squamous cell cancer (SCC) of the head and neck is controversial. In the current study, the authors evaluated the impact of high-risk HPV status on overall survival (OS) in patients with non-OPX SCC using a large database approach. METHODS:The National Cancer Data Base was queried to identify patients diagnosed from 2004 through 2014 with SCC of the OPX, hypopharynx (HPX), larynx, and oral cavity (OC) with known HPV status. Survival was estimated using Kaplan-Meier methods; distributions were compared using log-rank tests. Propensity score-matching and inverse probability of treatment weighing (IPTW) methods were used; cohorts were matched based on age, sex, Charlson-Deyo score, clinical American Joint Committee on Cancer (AJCC) group stage, treatments received, and anatomic subsite. Propensity analyses were stratified by group stage of disease. RESULTS:A total of 24,740 patients diagnosed from 2010 through 2013 were analyzed: 1085 patients with HPX, 4804 with laryngeal, 4,018 with OC, and 14,833 with OPX SCC. The percentages of HPV-positive cases by disease site were 17.7% for HPX, 11% for larynx, 10.6% for OC, and 62.9% for OPX. HPV status was found to be prognostic in multiple unadjusted and propensity-adjusted non-OPX populations. HPV positivity was associated with superior OS in patients with HPX SCC with a hazard ratio (HR) of 0.61 (P < .001 by IPTW), in patients with AJCC stage III to IVB laryngeal SCC (HR, 0.79; P = .019 by IPTW), and in patients with AJCC stage III to IVB OC SCC (HR, 0.78; P = .03 by IPTW). CONCLUSIONS:Positive high-risk HPV status appears to be associated with longer OS in multiple populations of patients with non-OPX head and neck disease (HPX, locally advanced larynx, and OC). If prospectively validated, these findings have implications for risk stratification.

SUBMITTER: Tian S

PROVIDER: S-EPMC6663628 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Survival outcomes by high-risk human papillomavirus status in nonoropharyngeal head and neck squamous cell carcinomas: A propensity-scored analysis of the National Cancer Data Base.

Tian Sibo S Switchenko Jeffrey M JM Jhaveri Jaymin J Cassidy Richard J RJ Ferris Matthew J MJ Press Robert H RH Pfister Neil T NT Patel Mihir R MR Saba Nabil F NF McDonald Mark W MW Higgins Kristin A KA Yu David S DS Curran Walter J WJ Gillespie Theresa W TW Beitler Jonathan J JJ

Cancer 20190423 16

<h4>Background</h4>The prognostic relevance of human papillomavirus (HPV) status in patients with nonoropharyngeal (OPX) squamous cell cancer (SCC) of the head and neck is controversial. In the current study, the authors evaluated the impact of high-risk HPV status on overall survival (OS) in patients with non-OPX SCC using a large database approach.<h4>Methods</h4>The National Cancer Data Base was queried to identify patients diagnosed from 2004 through 2014 with SCC of the OPX, hypopharynx (HP ...[more]

PMID: 31012957

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Project description:ImportanceAlthough the survival impact of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) is well known, there has been conflicting and scarce evidence on the role of HPV in non-OPSCC.ObjectiveTo undertake a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-compliant systematic review and meta-analysis of all published studies on the association between HPV status and survival outcomes in patients with non-OPSCC, analyzing each site separately.Data sourcesPubMed, CINAHL, and Embase were searched from 1946 to December 16, 2019, for English-language articles.Study selectionAnalysis comprised randomized clinical trials or observational studies that each included at least 10 patients with non-OPSCC in which the presence of HPV was analyzed, survival outcomes were reported, and a clinical follow-up of 1 year or more was performed. Studies excluded were those in which data on OPSCC and non-OPSCC were not distinguished between both cohorts and studies on patients with distant metastatic tumors at diagnosis. Final analysis included outcomes that were analyzed in at least 3 studies.Data extraction and synthesisTwo reviewers independently abstracted the data. Risk of bias was estimated with the Newcastle-Ottawa Scale. Meta-analysis was performed using the random-effects model.Main outcomes and measuresThe primary end point was overall survival (OS); secondary end points were disease-specific survival (DSS) and disease-free survival (DFS).ResultsOf the 3947 articles screened, a total of 22 observational and 2 randomized clinical trials were included in the analysis, representing 24 854 patients. In oral cavity locations, OS was not significantly associated with HPV positivity (hazard ratio [HR], 1.16; 95% CI, 0.83-1.61; I2 = 71%); however, HPV-positive tumors showed worse DFS (HR, 1.81; 95% CI, 1.12-2.91; I2 = 47%). Laryngeal and hypopharyngeal HPV-positive tumors were associated with improved OS (HR, 0.71; 95% CI, 0.54-0.92; I2 = 38% and HR, 0.60; 95% CI, 0.47-0.76; I2 = 0%), respectively, whereas, in nasopharyngeal locations HPV was not associated with OS (HR, 0.82; 95% CI, 0.49-1.38; I2 = 46%) or DSS (HR, 0.55; 95% CI, 0.22-1.42; I2 = 65%).Conclusions and relevanceIn this meta-analysis of 24 studies, HPV was associated with improved OS in laryngeal and hypopharyngeal locations but not in the oral cavity and the nasopharynx. This information may be useful for future clinical studies of laryngeal and hypopharyngeal tumors and whether HPV status should be incorporated in prognostication of patients with these cancers.

Project description:BackgroundAnatomical site is strongly associated with head and neck cancer etiology, and etiology and patient sociodemographic characteristics are prognostic factors for survival. It is not known whether the effects of these predictors persist over the postdiagnosis period or are strongest proximal to the time of diagnosis.MethodsUsing survival times and causes of death for 180,434 patients with head and neck cancer in the Surveillance, Epidemiology, and End Results cancer registry (1973-2015), the empirical cumulative incidences of cancer-specific death and other-cause death were calculated with a competing risks framework, and the time-dependent effects (hazard ratios) of anatomical tumor site (oropharynx, oral cavity, or hypopharynx/larynx), age, sex, race, and year of diagnosis on cancer-specific death and other-cause death, stratified by tumor stage, were estimated.ResultsAll effects were significantly time-varying (P < .001). Patients with nonoropharyngeal cancer had a higher hazard of cancer-specific death but a similar cumulative fraction of deaths because of a higher rate of death from other causes. Cancer-specific survival has not changed for patients with nonoropharyngeal cancer over the past decades but has improved since 2000 for patients with oropharyngeal cancer. The effects of age and sex on cancer survival were strongest proximal to the diagnosis, whereas the effect of race persisted over time.ConclusionsRecent improvements in survival for patients with oropharyngeal cancer may be due more to an increasing fraction of cancers attributable to human papillomavirus than to increasing treatment effectiveness. The prognostic strength of anatomical site and other predictors changes over the postdiagnosis period.Lay summaryIt is generally assumed that the effects of tumor and personal characteristics on the survival of patients with head and neck cancer are fixed over time, but this study shows that many factors are most important only in the first few years after diagnosis. Also, recent improvements in the survival of patients with head and neck cancer appear to benefit only patients with cancers of the oropharynx. The improvements may be due more to an increasing fraction of cancers caused by human papillomavirus (which generally have better outcomes) than to advances in head and neck cancer treatment overall.

Project description:Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of cancers. Collectively, HNSCC ranks sixth in incidence rate worldwide. Apart from classical risk factors like tobacco and alcohol, infection of human papillomavirus (HPV) is emerging as a discrete risk factor for HNSCC. HPV-positive HNSCC represent a distinct group of diseases that differ in their clinical presentation. These lesions are well-differentiated, occur at an early age, and have better prognosis. Epidemiological studies have demonstrated a specific increase in the proportions of the HPV-positive HNSCC. HPV-positive and HPV-negative HNSCC lesions display different disease progression and clinical response. For tumorigenic-transformation, HPV essentially requires a permissive cellular environment and host cell factors for induction of viral transcription. As the spectrum of host factors is independent of HPV infection at the time of viral entry, presumably entry of HPV only selects host cells that are permissive to establishment of HPV infection. Growing evidence suggest that HPV plays a more active role in a subset of HNSCC, where they are transcriptionally-active. A variety of factors provide a favorable environment for HPV to become transcriptionally-active. The most notable are the set of transcription factors that have direct binding sites on the viral genome. As HPV does not have its own transcription machinery, it is fully dependent on host transcription factors to complete the life cycle. Here, we review and evaluate the current evidence on level of a subset of host transcription factors that influence viral genome, directly or indirectly, in HNSCC. Since many of these transcription factors can independently promote carcinogenesis, the composition of HPV permissive transcription factors in a tumor can serve as a surrogate marker of a separate molecularly-distinct class of HNSCC lesions including those cases, where HPV could not get a chance to infect but may manifest better prognosis.

Dataset Information

Survival outcomes by high-risk human papillomavirus status in nonoropharyngeal head and neck squamous cell carcinomas: A propensity-scored analysis of the National Cancer Data Base.

Publications

Survival outcomes by high-risk human papillomavirus status in nonoropharyngeal head and neck squamous cell carcinomas: A propensity-scored analysis of the National Cancer Data Base.

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