Abstract
BackgoundOropharyngeal cancer (OPC) associated with human papilloma virus (HPV OPC) shows better treatment outcomes than non-HPV OPC. We investigated the expression of p53, β-tubulin, bcl-2 and ERCC 1, which are well-known biomarkers to predict the chemotherapy response, according to HPV status in OPC patients.MethodsPatients who treated with at least 2 cycles of induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced oropharyngeal cancer were reviewed. HPV PCR and immunohistochemical stain was done in paraffin embedded tumor tissue and evaluated the relation with the chemotherapy response and survival outcomes according to HPV status.ResultsSeventy-four patients were enrolled for this study and all patients received induction chemotherapy with docetaxel, 5-FU and cisplatin. After induction chemotherapy, complete response (CR) was shown in 22 patients (30%) and partial response (PR) in 46 patients (62%). HPV + was detected in 21 patients (28%), while 35 patients (47%) showed p16+ expression by IHC analysis. p16 positive patients showed better overall response, PFS and OS than p16 negative patients. p53 and class III beta-tubulin expression were significantly higher in HPV- and p16- than HPV + and p16+ patients. Conversely, bcl-2 expression was greater in HPV + or p16+ than HPV- or p16- patients. ERCC1 expression did not differ significantly according to HPV status. In multivariate analyses, early T stage (p = 0.036) and good PS (PS 0) (p = 0.029) showed a better 3Y-PFS rate, and low p53 expression (p = 0.012) and complete response after induction chemotherapy (p = 0.026) were highly associated with 3Y-OS rate. Low expression of p53 and p16 positive patients showed significantly prolonged OS than others (p = 0.010).ConclusionP53, class III beta-tubulin and bcl-2 were differently expressed in OPC according to HPV status and present study suggested the underlying mechanism of better response to chemotherapy in case of HPV OPC than non-HPV OPC. Among these biomarkers, p53 is the strongest prognostic marker in OPC and p53 in addition to p16 support the rationale to study of de-escalation strategy for OPC.
Highlights
Among the head and neck cancers, which are well known for their heterogeneity, oropharyngeal cancer (OPC) has been reevaluated because its pathogenesis is associated with human papilloma virus (HPV)
HPV OPC responds better to chemotherapy and radiotherapy, which can be in part explained by non-mutant TP53 [11,12], absence of field cancerization related to tobacco use and functional p53-mediated apoptotic pathways [13] unlike non-HPV OPC occurring in younger patients, which has fewer comorbidities and a better performance status
Inclusion criteria for this study were a diagnosis of squamous cell carcinoma, tumor stage III to IV according to the American Joint Committee on Cancer Staging [22], treatment with at least two cycles of induction DCF chemotherapy with or without following concurrent chemoradiotherapy (CCRT), evaluation of the response to induction chemotherapy, paraffin-embedded tumor tissue available at diagnosis and informed consent provided, a Karnofsky performance status (KPS) ≥70 at diagnosis, and sufficient organ function to undergo chemoradiotherapy (CRT)
Summary
Among the head and neck cancers, which are well known for their heterogeneity, oropharyngeal cancer (OPC) has been reevaluated because its pathogenesis is associated with human papilloma virus (HPV). HPV OPC may have different epidemiological and histopathological characteristics than other head and neck cancers, which are usually associated with smoking and alcohol use [7,8]. Non-HPV OPC is associated with smoking-induced multistep carcinogenesis, such as frequent TP53 mutations and p16 impairment [10]. HPV OPC responds better to chemotherapy and radiotherapy, which can be in part explained by non-mutant TP53 [11,12], absence of field cancerization related to tobacco use and functional p53-mediated apoptotic pathways [13] unlike non-HPV OPC occurring in younger patients, which has fewer comorbidities and a better performance status. Biomarkers for chemotherapy response in OPC according to HPV status have not been identified
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