title: The prevalence of human papillomavirus in squamous cell carcinoma of unknown primary site metastatic to neck lymph nodes: a systematic review.
abstract: A subset of head and neck squamous cell carcinoma, which mainly arise from the crypt epithelium of the palatine and lingual tonsils, may be caused by high-risk human papillomavirus (HPV) infections. This topographical restriction together with other overlapping clinical features have led investigators to suspect that HPV plays a role in squamous cell carcinoma of unknown primary (SCCUP) site metastatic to neck lymph nodes. We performed a systematic review of articles listed in PubMed to identify studies testing HPV and/or p16(INK4a) status (p16) in tissue samples from initial and definitive SCCUP. The prevalence of HPV-related (HPV DNA-positive and/or p16 positive) SCCUP was calculated for all the SCCUP, initial SCCUP, suspected definitive SCCUP, and true definitive SCCUP whenever a minimum of 10 cases of each category was identified. In addition, data concerning patients' diagnostic work-up, the HPV detection methods, and the correlations between HPV-status, the localization of the occult primary tumor, and the clinical outcome were also extracted. Eighteen retrospective cohort studies, assessing a total of 659 patients, met the inclusion criteria. The overall median prevalences of HPV-DNA(pos), of p16(pos), and of positivity for both HPV markers were, respectively, 37.0, 48.5, and 36.0 %. Patients with diagnosis of initial SCCUP had overall median prevalences of HPV-DNA(pos), of p16(pos), and of positivity for both HPV markers, respectively, of 81.8, 86.2, and 80.8 %. The data uncovered by this systematic review confirm that SCCUP is frequently causally associated to HPV-driven oropharyngeal squamous cell carcinomas. This finding supports the view that HPV-status could be routinely assessed in SCCUP patients as it may lead to identifying the primary tumor and the decision to de-escalate treatment.
authors.affiliation: Department of Neurosciences, Regional Center for Head and Neck Cancer, University of Padua, P.le Ospedale 1, 31100, Treviso, Italy. paolo.boscolorizzo@unipd.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Boscolo-Rizzo
authors.affiliation: Division of Molecular Diagnostics of Oncogenic Infections, Research Program Infection and Cancer, German Cancer Research Center (DKFZ), F020, Heidelberg, Germany.
authors.forename: Lea
authors.initials: L
authors.lastname: Schroeder
authors.affiliation: Department of Pathology, Treviso Regional Hospital, Treviso, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Romeo
authors.affiliation: Division of Molecular Diagnostics of Oncogenic Infections, Research Program Infection and Cancer, German Cancer Research Center (DKFZ), F020, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D006801:Humans; D008207:Lymphatic Metastasis; D009333:Neck; D009382:Neoplasms, Unknown Primary / Q000473:pathology / Q000821:virology*; D027383:Papillomaviridae / Q000302:isolation & purification*
chemical_list: D004279:DNA, Viral
keywords: HPV; Head neck cancer; Human papillomavirus; Squamous cell carcinoma; Unknown primary; p16