title: Increasing prevalence rates of HPV attributable oropharyngeal squamous cell carcinomas in the Netherlands as assessed by a validated test algorithm.
abstract: Human papillomavirus (HPV) infection has been etiologically linked to oropharyngeal squamous cell carcinoma (OPSCC). The prevalence of HPV-positive OPSCC varies between studies, ranging from 20 to 90%. This may be related to the lack of a standardized HPV detection assay as well as to the time period in which HPV prevalence is investigated, as rising incidence rates are reported over the last decades. Here, we validated our previously defined test algorithm for HPV detection in formalin-fixed paraffin-embedded (FFPE) tumor specimen consisting of p16(INK4A)  immunostaining followed by high-risk HPV DNA detection by GP5+/6+ PCR on the positive cases (Smeets et al., Int J Cancer 2007;121:2465-72). In addition, we analyzed HPV prevalence rates in OPSCCs in the years 1990-2010. The test algorithm was validated on a consecutive series of 86 OPSCCs collected during 2008-2011, of which both fresh frozen and FFPE samples were available. We performed HPV-E6 RT-PCR on the frozen samples as gold standard and applied the algorithm to the corresponding FFPE samples. The test algorithm showed an accuracy of 98%. Using the validated algorithm, we determined the presence of an oncogenic HPV infection in 240 OPSCCs of patients diagnosed in the years 1990-2010 at our center. A significant increase in the proportion of HPV-positive samples was observed, from 5.1% in 1990 to 29.0% in 2010 (p = 0.001). In conclusion, we confirmed the accuracy of the test algorithm for HPV detection in FFPE tumor specimen and we found a significant increase in the prevalence of HPV in OPSCC over the last two decades at our center.
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Rietbergen
authors.forename: C René
authors.initials: CR
authors.lastname: Leemans
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bloemena
authors.forename: Daniëlle A M
authors.initials: DA
authors.lastname: Heideman
authors.forename: Boudewijn J M
authors.initials: BJ
authors.lastname: Braakhuis
authors.forename: Albertus T
authors.initials: AT
authors.lastname: Hesselink
authors.forename: Birgit I
authors.initials: BI
authors.lastname: Witte
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Baatenburg de Jong
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.forename: Ruud H
authors.initials: RH
authors.lastname: Brakenhoff
mesh_terms: D000465:Algorithms; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology*; D015331:Cohort Studies; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D009959:Oropharyngeal Neoplasms / Q000473:pathology / Q000821:virology*; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000453:epidemiology / Q000821:virology; D016612:Paraffin Embedding; D015995:Prevalence; D011379:Prognosis; D014412:Tumor Virus Infections / Q000175:diagnosis* / Q000453:epidemiology / Q000821:virology; D019562:Viral Load
chemical_list: D004279:DNA, Viral