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Background: Human papillomavirus-associated oropharynx squamous cell carcinoma (HPV-OPSCC) has no known pre-malignant lesion. While vaccination offers future primary prevention, there is current interest in secondary prevention. The feasibility of clinical evaluation of individuals at increased risk for HPV-OPSCC is unclear., Methods: Individuals with risk factors for HPV-OPSCC were enrolled in a prospective study (MOUTH). Participants positive for biomarkers associated with HPV-OPSCC were eligible for a clinical evaluation which comprised a head and neck examination and imaging with ultrasound and/or magnetic resonance imaging (MRI). This study was designed to evaluate feasibility of clinical evaluation in a screening study., Results: Three hundred and eighty-four participants were eligible for clinical evaluation. Of the 384, 204 (53%) completed a head and neck examination or imaging. Of these, 66 (32%) completed MRI (n = 51) and/or ultrasound (n = 64) studies., Conclusions: Clinical evaluations, including head and neck examination and imaging, are feasible in the context of a screening study for HPV-OPSCC., (© 2022 Wiley Periodicals LLC.)

Lip and oral cavity squamous cell carcinoma (SCC) develop from progressive dysplasia of these mucosal structures. The cancers are often preceded by premalignant lesions, and any nonhealing ulcers of the lip or oral cavity should be biopsied. Some risk factors for these 2 subsites overlap and include tobacco use, alcohol use, and an immunocompromised state. Lip and oral cavity SCC are clinically staged based on physical examination and imaging. The 5-year overall survival for early-stage lip and oral cavity SCC is around 70% to 90% but decreases to about 50% for late-stage disease., Competing Interests: Disclosure Nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Patients with HPV+ oropharyngeal squamous cell carcinoma were assigned to dose and volume de-escalated radiotherapy (RT) or chemoradiotherapy (CRT) based on response to induction chemotherapy in an effort to limit treatment-related toxicity while preserving efficacy., Patients and Methods: Patients were classified as low-risk (≤T3, ≤N2B, ≤10 pack-year history) or high-risk (T4 or ≥N2C or >10 PYH). After three cycles of carboplatin/nab-paclitaxel, response was assessed using Response Evaluation Criteria in Solid Tumors 1.1. Low-risk patients with ≥50% response received 50 Gray (Gy) RT (RT50) while low-risk patients with 30%-50% response or high-risk patients with ≥50% response received 45 Gy CRT (CRT45). Patients with lesser response received standard-of-care 75 Gy CRT (CRT75). RT/CRT was limited to the first echelon of uninvolved nodes. The primary end point was 2-year progression-free survival compared with a historic control of 85%. Secondary end points included overall survival and toxicity., Results: Sixty-two patients (28 low risk/34 high risk) were enrolled. Of low-risk patients, 71% received RT50 while 21% received CRT45. Of high-risk patients, 71% received CRT45. With a median follow-up of 29 months, 2-year PFS and OS were 95% and 100% for low-risk patients and 94% and 97% for high-risk patients, respectively. The overall 2-year PFS was 94.5% and within the 11% noninferiority margin for the historic control. Grade 3+ mucositis occurred in 30%, 63%, and 91% of the RT50, CRT45, and CRT75 groups, respectively (P = 0.004). Rates of any PEG-tube use were 0%, 31%, and 82% for RT50, CRT45, and CRT75 groups, respectively (P < 0.0001)., Conclusions: Induction chemotherapy with response and risk-stratified dose and volume de-escalated RT/CRT for HPV+ OPSCC is associated with favorable oncologic outcomes and reduced acute and chronic toxicity. Further evaluation of induction-based de-escalation in large multicenter studies is justified., Clinical Trial Registration: Clinical trials.gov identifier: NCT02258659., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Definitive chemoradiation (CRT) for oral cavity squamous cell carcinoma (OC-SCC) is often criticized for poor efficacy or toxicity. We describe a favorable 20-year experience of primary CRT for locally-advanced OC-SCC., Materials and Methods: Patients with locally-advanced, stage III/IV OC-SCC receiving primary concomitant CRT on protocols from 1994 to 2014 were analyzed. Chemotherapy included fluorouracil and hydroxyurea with other third agents. Radiotherapy (RT) was delivered once or twice daily to a maximum dose of 70-75 Gy. Intensity-modulated RT (IMRT) was exclusively used after 2004. Progression-free survival (PFS), overall survival (OS), locoregional control (LRC), and distant control (DC) were calculated by the Kaplan-Meier method and compared across treatment decades using the log-rank test. Rates of osteoradionecrosis (ORN) requiring surgery were compared across treatment decades using the Chi-square test., Results: 140 patients with locally-advanced OC-SCC were treated with definitive CRT. Of these, 75.7% had T3/T4 disease, 68.6% had ≥N2 nodal disease, and 91.4% had stage IV disease. Most common primary sites were oral tongue (47.9%) and floor of mouth (24.3%). Median follow-up was 5.7 years. Five-year OS, PFS, LRC, and DC were 63.2%, 58.7%, 78.6%, and 87.2%, respectively. Rates of ORN and long-term feeding tube dependence were 20.7% and 10.0%, respectively. Differences in LRC (P = 0.90), DC (P = 0.24), PFS (P = 0.38), OS (P = 0.10), or ORN (P = 0.38) were not significant across treatment decades., Conclusion: Definitive CRT is a viable and feasible strategy for organ preservation for patients with locally-advanced OC-SCC., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

To evaluate the incidence of a subsequent primary thyroid malignancy in patients with an index head and neck squamous cell carcinoma (HNSCC), we analyzed the National Cancer Institute's Surveillance, Epidemiology, and End Results database to identify a cohort of patients who had been diagnosed with a primary HNSCC from 1973 through 2004. The study population was made up of 60,323 patients of all ages, roughly three-quarters of whom were male. A total of 60 patients (0.1%) developed a subsequent thyroid malignancy-not a statistically significant finding. The overall standard incidence ratio (SIR) for a subsequent thyroid malignancy was 1.58 (p < 0.05). The highest SIRs were seen during in the first 5 years after diagnosis of the original primary (SIR: 3.05; p < 0.05), more specifically in 2 to 11 months after diagnosis (SIR: 7.11; p < 0.05). Further analyses demonstrated that SIRs were significantly higher in males (SIR: 1.71), in patients aged 60 through 79 years (SIR: 1.71), in whites (SIR: 1.55), in patients who had undergone external-beam radiotherapy for their index primary (SIR: 1.84), in those whose tumor was initially staged as regional (SIR: 1.96), and in patients whose index primary was in the oral cavity (SIR: 1.71) or larynx (SIR: 1.88) (p < 0.05 for all). We conclude that the incidence of a subsequent primary thyroid malignancy in patients with an HNSCC is highest during the first 5 years after diagnosis of the index primary, reflecting the benefit of continued surveillance.

Background: Evidence suggests the incidence of oral tongue squamous cell carcinoma is increasing in young patients, many who have no history of tobacco use., Methods: We clinically reviewed 89 patients with oral tongue cancer. Exomic sequencing of tumor DNA from 6 nonsmokers was performed and compared to previously sequenced cases. RNA from 20 tumors was evaluated by massively parallel sequencing to search for potentially oncogenic viruses., Results: Non-smokers (53 of 89) were younger than smokers (36 of 89; mean, 50.4 vs 61.9 years; p < .001), and seemed more likely to be women (58.5% vs 38.9%; p = .069). Nonsmokers had fewer TP53 mutations (p = .02) than smokers. No tumor-associated viruses were detected., Conclusion: The young age of nonsmoking patients with oral tongue cancer and fewer TP53 mutations suggest a viral role in this disease. Our efforts to identify such a virus were unsuccessful. Further studies are warranted to elucidate the drivers of carcinogenesis in these patients., (© 2014 Wiley Periodicals, Inc.)