title: Absent/weak CD44 intensity and positive human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma indicates a very high survival.
abstract: Patients with human papillomavirus DNA positive (HPV(DNA+)) oropharyngeal squamous cell carcinoma (OSCC) have better clinical outcome than those with HPV DNA negative (HPV(DNA-)) OSCC upon intensive oncological treatment. All HPV(DNA+) OSCC patients may not require intensive treatment, however, but before potentially deintensifying treatment, additional predictive markers are needed. Here, we examined HPV, p16(INK4a), and CD44 in OSCC in correlation to clinical outcome. Pretreatment tumors from 290 OSCC patients, the majority not receiving chemotherapy, were analyzed for HPV DNA by Luminex and for p16(INK4a) and CD44 by immunohistochemistry. 225/290 (78%) tumors were HPV(DNA+) and 211/290 (73%) overexpressed p16(INK4a), which correlated to presence of HPV (P < 0.0001). Presence of HPV DNA, absent/weak CD44 intensity staining correlated to favorable 3-year disease-free survival (DFS) and overall survival (OS) by univariate and multivariate analysis, and likewise for p16(INK4a) by univariate analysis. Upon stratification for HPV, HPV(DNA+) OSCC with absent/weak CD44 intensity presented the significantly best 3-year DFS and OS, with >95% 3-year DFS and OS. Furthermore, in HPV(DNA+) OSCC, p16(INK4a)+ overexpression correlated to a favorable 3-year OS. In conclusion, patients with HPV(DNA+) and absent/weak CD44 intensity OSCC presented the best survival and this marker combination could possibly be used for selecting patients for tailored deintensified treatment in prospective clinical trials.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Näsman
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nordfors
authors.forename: Nathalie
authors.initials: N
authors.lastname: Grün
authors.forename: Eva
authors.initials: E
authors.lastname: Munck-Wikland
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Ramqvist
authors.forename: Linda
authors.initials: L
authors.lastname: Marklund
authors.forename: David
authors.initials: D
authors.lastname: Lindquist
authors.forename: Tina
authors.initials: T
authors.lastname: Dalianis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000628:therapy / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004279:DNA, Viral; D005260:Female; D015870:Gene Expression; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009959:Oropharyngeal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy / Q000821:virology*; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000150:complications*; D063868:Patient Outcome Assessment; D011379:Prognosis
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D018960:Hyaluronan Receptors
keywords: CD44; human papillomavirus; oropharyngeal cancer; prognosis