title: Cancer of unknown primary originating from oropharyngeal carcinomas are strongly correlated to HPV positivity.
abstract: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OSCC) has been identified as a distinct entity within squamous cell carcinoma of the head and neck. It is associated with special characteristics and is preponderantly restricted to palatial tonsils and base of tongue. These primary locations have for long been associated with the clinical situation of cancer of unknown primary (CUP). In order to investigate the putative relationship between CUP and HPV, we investigated 26 patients who initially presented as CUP and were finally diagnosed with carcinomas of these two locations. Twenty-one cases proved to be positive for high-risk HPV. Primary carcinomas were small and frequently presented in a submucosal location. HPV-positive carcinomas, presented more often in women, showed atypical basaloid differentiation and correlated to cystic lymph node metastases. This study demonstrates an over-representation of HPV-associated OSCC in patients who were initially diagnosed with CUP. This finding indicates a strong relationship between HPV-association and CUP in OSCC. The frequent manifestation as CUP is presumably caused by the unusual predisposition for small size and submucosal location combined with early lymphatic metastization. In order not to miss clinically occult carcinomas, consequent interdisciplinary cooperation in combination with meticulous histological workup is mandatory.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Grosshadern Medical Center, Ludwig Maximilian University, Marchioninistrasse 15, 81377 Munich, Germany. pamela.zengel@med.uni-muenchen.de
authors.forename: Pamela
authors.initials: P
authors.lastname: Zengel
authors.forename: Gerald
authors.initials: G
authors.lastname: Assmann
authors.forename: Martin
authors.initials: M
authors.lastname: Mollenhauer
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.forename: Karl
authors.initials: K
authors.lastname: Sotlar
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.forename: Stephan
authors.initials: S
authors.lastname: Ihrler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D052685:Alphapapillomavirus / Q000302:isolation & purification*; D002294:Carcinoma, Squamous Cell / Q000556:secondary* / Q000821:virology; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000473:pathology* / Q000821:virology; D009959:Oropharyngeal Neoplasms / Q000473:pathology* / Q000821:virology; D014066:Palatine Tonsil / Q000473:pathology / Q000821:virology; D030361:Papillomavirus Infections / Q000473:pathology* / Q000821:virology; D012189:Retrospective Studies; D014059:Tongue / Q000473:pathology / Q000821:virology