Abstract

Patients with human papillomavirus DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) have better clinical outcome than those with HPV DNA negative (HPVDNA−) OSCC upon intensive oncological treatment. All HPVDNA+ OSCC patients may not require intensive treatment, however, but before potentially deintensifying treatment, additional predictive markers are needed. Here, we examined HPV, p16INK4a, 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 p16INK4a and CD44 by immunohistochemistry. 225/290 (78%) tumors were HPVDNA+ and 211/290 (73%) overexpressed p16INK4a, 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 p16INK4a by univariate analysis. Upon stratification for HPV, HPVDNA+ OSCC with absent/weak CD44 intensity presented the significantly best 3-year DFS and OS, with >95% 3-year DFS and OS. Furthermore, in HPVDNA+ OSCC, p16INK4a+ overexpression correlated to a favorable 3-year OS. In conclusion, patients with HPVDNA+ 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.Absence of/weak CD44 or presence of human papillomavirus (HPV) DNA was shown as a favorable prognostic factors in tonsillar and tongue base cancer. Moreover, patients with the combination of absence of/weak CD44 and presence of HPV DNA presented a very favorable outcome. Therefore, we suggest that this marker combination could potentially be used to single out patients with a high survival that could benefit from a de-escalated oncological treatment.

Highlights

  • Recent reports from several countries indicate an increased incidence of oropharyngeal squamous cell carcinoma (OSCC) [1,2,3,4,5], where tonsillar squamous cell carcinoma (TSCC) and base of tongue squamous cell carcinoma (BOTSCC) dominate

  • Many patients with HPVDNA+ OSCC may not benefit from this intensified treatment, and could potentially be cured by radiotherapy (RT) alone, with possibly less severe sequele

  • human papillomavirus (HPV)+ and HPV OSCC, where 80% of the patients did not receive chemotherapy, we have evaluated CD44 intensity staining and p16INK4a in relationship to HPV status and in relation to overall survival (OS) and disease-free survival (DFS)

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Summary

Introduction

Recent reports from several countries indicate an increased incidence of oropharyngeal squamous cell carcinoma (OSCC) [1,2,3,4,5], where tonsillar squamous cell carcinoma (TSCC) and base of tongue squamous cell carcinoma (BOTSCC) dominate. This increase has mainly been attributed to human papillomavirus (HPV) infection [2]. Patients with HPV DNA positive (HPVDNA+) OSCC have been reported to have a better. Slides were developed in chromogen 3’-diaminobenzydine (DAB) (Vector Laboratories) with hematoxylin as a counter stain

Evaluation of immunohistochemistry staining
Results
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