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Objective: The causative and prognostic roles of human papillomavirus (HPV) in non-oropharyngeal squamous cell carcinoma of the head and neck are uncertain. This umbrella review assessed the strength and quality of evidence and graded the evidence derived from published meta-analyses on this subject. Data sources: MEDLINE, Embase, and the Cochrane Library were searched. Meta-analyses of observational studies and randomized trials were included. Review methods: Evidence of association was graded according to the established criteria: strong, highly suggestive, suggestive, weak, or not significant. Results: 15 meta-analyses were evaluated. The association with HPV was highly suggestive of oral (OR = 2.40, [1.87–3.07], P < 0.00001) and nasopharyngeal cancers (OR = 17.82 [11.20–28.35], P < 0.00001). Improved survival emerged only in hypopharyngeal carcinoma and was confirmed in studies in which only p16 + cancers were considered. Conclusion: HPV infection may increase the risk of oral cavity and nasopharyngeal cancer. However, the prognosis was not influenced, except in hypopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is rapidly evolving. Despite either surgery or radiotherapy (RT), with or without chemotherapy (CT), being acceptable in intermediate and locally advanced diseases, there is uncertainty regarding the best treatment option for these patients. Therefore, we performed a network meta-analysis (NMA) to compare the relative efficacy of different treatments for HPV+ oropharyngeal carcinoma. Material and methods: Randomized clinical trials that enrolled adults with non-metastatic HPV+ oropharynx cancer and provided data about overall survival (OS) and/or progression-free survival (PFS) and/or locoregional control and distant metastases (LRC and DM) were included. Fixed- or random-effects models were fit using a Bayesian approach to NMA. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (CrIs). The primary outcome was OS. Results: A total of 844 citations were screened; 11 randomized clinical trials were included (HPV+ stage III–IV cancer, mainly oropharynx carcinomas). Nine treatment arms were compared. Radiotherapy (altered or standard fractionation) + triweekly cisplatin (HR 3.8; 95% CrIs 0.29–65 and 0.3; 95% CrIs 0.03–2.51) was superior to RT in term of OS (P score = 0.42 and 0.16). Radiotherapy with low and high cisplatin doses appeared similar (HR 1.57; 95% CrIs 0.19–12.72). Altered fractionation or standard RT + 3-weekly cisplatin are the 2 highest-ranked options in terms of PFS (P score = 0.35 and 0.34). Conclusions: This meta-analysis confirms the role of cisplatin added to RT as the best option for HPV+ oropharyngeal carcinoma. RT+ 3-weekly cisplatin is likely to be the best radical treatment in terms of OS and PFS. [ABSTRACT FROM AUTHOR]