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Background The optimal imaging for the staging of oropharyngeal cancer is not well defined. Methods The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database for 2006 through 2011 was used to compare patient characteristics and hospital region by the initial imaging modality used for patients with oropharyngeal cancer. The primary outcome was 3-year cancer-specific survival (CSS). Cox proportional hazards models were adjusted for imaging, age, sex, region, education, race, American Joint Committee on Cancer stage of disease, and treatment, which were examined using backward elimination. The authors also explored how initial imaging use varied by patient characteristics and hospital region. Results A total of 1765 patients underwent initial diagnostic imaging. Of those, approximately 11.4% (202 patients) received computed tomography (CT) alone as their initial imaging modality, 5.2% (91 patients) underwent magnetic resonance imaging (MRI) without positron emission tomography (PET), and 83.3% (1472 patients) had initial imaging that included PET. The overall 3-year CSS rate for the entire population was 63.7%. In the adjusted survival models compared by initial imaging modality, patients who underwent a PET examination were found to have higher survival than those who underwent CT alone or MRI, respectively (hazard ratio, 1.337 [95% CI, 1.001-1.785; P = .0491]; and hazard ratio, 1.748 [95% CI, 1.2-2.545; P = .0036]). Conclusions Among patients with oropharyngeal cancer, initial staging with PET imaging was associated with improved 3-year CSS compared with initial staging with MRI or CT.

BACKGROUND Favorable outcomes for human papillomavirus–associated oropharyngeal cancer have led to interest in identifying a subgroup of patients with the lowest risk of disease recurrence after therapy. De-intensification of therapy for this group may result in survival outcomes that are similar to those associated with current therapy but with less toxicity. To advance this effort, this study analyzed the outcomes of oropharyngeal cancer patients treated with or without systemic therapy. METHODS This was a retrospective study of patients with oropharyngeal cancer treated between 1985 and 2012. The criteria for inclusion were ≤10 pack-years of cigarette smoking and stage III/IVA cancer limited to T1-3, N1-N2b, and T3N0 disease. A survival analysis was performed with the primary endpoint of progression-free survival (PFS). RESULTS The cohort included 857 patients. Systemic therapy was given to 439 patients (51%). The median survival was 80 months. The 2-year PFS rate was 91%. When the analysis was limited to 324 patients irradiated without systemic therapy, the 2- and 5-year PFS rates were 90% and 85%, respectively. Furthermore, for these 324 patients, the 5-year PFS rates for T1, T2, and T3 disease were 90%, 83%, and 70%, respectively. The 5-year PFS rate for patients treated with systemic therapy for T3 disease was 77% (P = .07). CONCLUSIONS According to the low-risk definition currently established in cooperative trials, the patients had a 2-year PFS rate approximating 90%. When patients who were treated with radiation alone were evaluated, no compromise was observed in this high rate of PFS, which is higher than the 2-year PFS thresholds used in current cooperative trials. Cancer 2016. © 2016 American Cancer Society.

BACKGROUND The incidence of oropharyngeal squamous cell carcinoma caused by oncogenic HPV (HPV-OPSCC) is rising worldwide. HPV-OPSCC is commonly diagnosed by RT-qPCR of HPV-16 E6 and E7 oncoproteins or by cyclin-dependent kinase inhibitor 2A, multiple tumor suppressor 1 (p16) immunohistochemistry (IHC). Droplet digital PCR (ddPCR) has been recently reported as ultra-sensitive and highly precise method of nucleic acid quantification for biomarker analysis. We aimed to validate this method for the detection of HPV-16 E6 and E7 in HPV-OPSCC. METHODS Participants were recruited from January 2015-November 2015 at initial presentation to the University of Alberta Head and Neck Oncology Clinic. RNA was extracted, purified and quantified from prospectively collected participant tissues, and ddPCR was performed with fluorescent probes detecting HPV-16 E6 and E7. Results from ddPCR were compared with p16 IHC performed by clinical pathology as standard of care. RESULTS Head and neck tissues were prospectively obtained from 68 participants including 29 patients with OPSCC, 29 patients with non-OPSCC and 10 patients without carcinoma. 79.2% of patients with OPSCC were p16 positive. The sensitivity and specificity of ddPCR HPV E6/E7 compared with p16 IHC in OPSCC was 91.3 and 100%, respectively. The amount of target RNA used was ≤1 ng, 20-50 times lower than reported by other for RT-qPCR HPV E6/E7. CONCLUSIONS The ddPCR of HPV E6/E7 is a novel and highly specific method of detecting HPV-16 in OPSCC. Cancer 2016. © 2016 American Cancer Society.

BACKGROUND The current head and neck squamous cell carcinoma (HNSCC) staging system may not capture the full prognostic implications of regional lymph node involvement. This study investigated the impact of the level of lymph node metastasis (LNM) on survival. METHODS The Surveillance, Epidemiology, and End Results registry was queried for oral cavity (OC), oropharynx (OP), larynx (LAR), and hypopharynx (HP) HNSCC. A multivariate Cox proportional hazards model was used to evaluate whether the level of LNM was an independent prognostic factor. Site-specific recursive-partitioning analysis was performed to classify patients into different risk groups. RESULTS In all, 14,499 patients, including OC (n = 2463), OP (n = 8567), LAR (n = 2332), and HP patients (n = 1137), were analyzed. Both the American Joint Committee on Cancer (AJCC) N classification and the level of LNM showed significant effects on overall survival (OS) in patients with OC, OP, or LAR HNSCC but not in patients with HP HNSCC. In patients with N2 disease, the AJCC subclassification (N2a, N2b, or N2c) was significantly associated with the OS of patients with OP and LAR HNSCC but not with the OS of patients with OC or HP HNSCC, whereas the level of LNM (primary, secondary, or tertiary) was significantly associated with the OS of patients with OC, OP, and LAR HNSCC but not HP HNSCC. With recursive-partitioning analysis, a simple, primary site–specific prognostic tool integrating the AJCC T and N classifications and the level of LNM was designed, and it could be easily used by health care providers in clinic. CONCLUSIONS The level of LNM is an independent prognostic factor for patients with locally advanced HNSCC and could add to the prognostic value of AJCC T and N classifications in patients with locally advanced HNSCC. Cancer 2016;122:534–545. © 2015 American Cancer Society.

The National Comprehensive Cancer Network (NCCN) describes the presence of extracapsular spread and/or positive margins in oropharynx cancer (OPC) as an indication for the addition of chemotherapy to postoperative radiation. The guideline's category 1 consensus is based on what they term high-level evidence. For this study, the authors performed a critical appraisal of the research upon which the NCCN guideline is based and assessed its relevance in the era of human papillomavirus (HPV)/p16-positive OPC. Multiple shortcomings were identified, including patient exclusion after randomization and the use of unplanned subgroup analyses without multivariate adjustment, which undermined internal validity. Indeterminate HPV/p16 status limited external validity. Given the unique biology of HPV/p16-positive tumors and the problems of internal and external validity, the authors concluded that the literature upon which the recommendation for the addition of chemotherapy to adjuvant radiation was based does not generate high-level evidence, and its relevance for the postoperative management of patients with HPV/p16-positive OPC remains unknown.

BACKGROUND A recent review of the Surveillance, Epidemiology, and End Results registry suggested that patients with index squamous cell carcinoma (SCC) of the oropharynx (SCCOP) are less likely to develop second primary malignancies (SPM) than patients with index SCC of nonoropharyngeal sites (oral cavity, larynx, hypopharynx). The objectives of this study were to determine the impact of index primary tumor site on SPM risk and to explore factors that potentially affect this risk within a large, prospectively accrued cohort of patients with index SCC of the head and neck (SCCHN). METHODS A cohort of 2230 patients with incident SCCHN was reviewed for development of SPM. Kaplan-Meier analysis, log-rank testing, and Cox proportional hazards models were used to detect the impact of various factors, including index tumor site, on SPM risk. RESULTS The SPM rate was lower for patients with index SCCOP than for patients with index nonoropharyngeal cancer (P

Unlike most other types of head and neck cancer, oropharyngeal squamous cell carcinoma (SCC) has many unique characteristics, including its strong association with human papillomavirus (HPV) infection 1. Epidemiologic studies indicate that HPV-positive oropharyngeal cancer occurs commonly in patients of younger age, with higher numbers of sex partners, more oral sex exposure, and lower smoking rates 1–4. Previous studies also show that oropharyngeal cancer patients with HPV infection generally have more favorable outcome compared to those without HPV infection 3–7. However, the molecular mechanisms underlying this divergence in disease outcome are largely unknown. Although the overall incidence of head and neck cancer has decreased steadily in the past decades, the number of reported oropharyngeal cancer cases has increased significantly 8, 9. Thus, there is an urgent need to focus specifically on oropharyngeal cancer to determine its unique characteristics with the goal of developing specific and targeted treatments. Currently, oncologists rely primarily on tumor stage to make treatment decisions for oropharyngeal cancer. In recent years, the HPV status of oropharyngeal cancer has also been proposed as a promising prognostic marker and treatment factor 3–7. In this study, we investigated the prognostic value of microRNAs (miRNAs) for oropharyngeal cancer. miRNAs are a family of small non-coding RNAs that suppress the expression of their gene targets 10. About one thousand human miRNAs have been identified to date. Both computational and experimental studies indicate that thousands of human protein-coding genes are directly regulated by miRNAs 11–13. Thus, miRNAs function as master regulators for many important biological processes, including cell growth, apoptosis, viral infection, cancer initiation and progression 10, 14–17. Previous studies show that miRNA expression signatures are promising biomarkers for the diagnosis and prognosis of a wide array of human cancers 18, 19. However, the prognostic value of miRNAs in oropharyngeal cancer has not been investigated to date. Relevant to our study, recent studies show that miRNAs are aberrantly expressed in head and neck cancer cell lines as well as in tumor tissues as compared to normal tissues 20–24. In addition, altered miRNA expression has also been reported in relation to HPV expression in cancer cell lines 25. These miRNA studies focused primarily on the early diagnosis of head and neck cancer, but not the prediction of disease outcome. More importantly, all these studies were performed using heterogeneous tumor tissues or cell lines from multiple types of head and neck cancer. It is now evident that oropharyngeal cancer has many unique characteristics that are distinct from other head and neck cancers. Thus, these published results may not be applicable to oropharyngeal cancer. To avoid these pitfalls, we focused our miRNA analysis exclusively on oropharyngeal SCC.

BACKGROUND: The p53 pathway plays a critical role in maintaining genomic stability and preventing tumor formation. Given the roles of both MDM4 and HPV16 E6 oncoproteins in inhibition of p53 activity, we tested the hypothesis that MDM4 polymorphisms are associated with the risk of HPV16-associated squamous cell carcinoma of head and neck (SCCHN). METHODS: Genotyping was conducted on 3 tagging single nucleotide polymorphisms (rs11801299 G>A, rs10900598 G>T, and rs1380576 C>G) in MDM4, and serology was used to determine HPV 16 exposure in 380 cases and 335 cancer-free controls that were frequency-matched by age, sex, smoking, and drinking status. RESULTS: None of 3 MDM4 polymorphisms alone was significantly associated with risk of overall SCCHN. With further analysis stratified by HPV16 serology and tumor site, we found that each polymorphism individually modified the risk of HPV16-associated squamous cell carcinoma of the oropharynx (SCCOP), and such effect modification was particularly pronounced in never smokers and never drinkers. CONCLUSION: The risk of HPV16-associated SCCOP could be modified by MDM4 polymorphisms. Large and prospective studies are needed to validate our findings. Cancer 2011;. © 2011 American Cancer Society.

Most squamous cell carcinomas of the oral cavity and oropharynx are not diagnosed until they have attained at least the T2 stage (greater than 2.0 cm). This study identifies factors which may contribute to the delayed diagnosis of these tumors, despite the fact that they frequently arise at sites readily accessible to examination. Personal interviews of 149 patients with oral and oropharyngeal squamous cell carcinoma revealed delays by patients of one day to more than one year (mean, 17 weeks) before seeking care. Furthermore, delay by doctors occurred in 45 instances (30%). Neither short nor long delays had a statistically significant relationship to tumor T stage at the time of diagnosis. The length of patient delay was also not related to age, gender, amount of education, or history of alcohol consumption. The authors concluded that the early carcinomas were probably asymptomatic and subsequent manifestations were commonly misinterpreted as benign or innocuous oral/dental problems. These inconspicuous or misleading perceptions may be primarily responsible for the advanced stages of these tumors at the time of discovery. Emphasis must, therefore, be placed upon gaining access to high-risk individuals for periodic oral and oropharyngeal examinations and upon educational efforts to increase the skill of primary health care providers in recognizing this problem.