Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. A special entity among HNSCCs is HPV-associated oropharyngeal cancer (OPC) with p16 positivity as a surrogate marker of cancer’s viral etiology. A standard of definitive treatment for these tumors is cisplatin (CDDP) given concurrently with radiotherapy (RT). Another possible option being investigated is replacement of CDDP with cetuximab (C225). However, the optimal treatment for HPV-positive OPC remains unclear, until ongoing studies provide more evidence on this matter. The aim of this meta-analysis is to provide guidance regarding treatment decision-making in this subgroup of patients.
We performed a systematic literature search using the MEDLINE, PubMed, EMBASE, Web of Science, ScienceDirect, and Scopus databases. Meta-analysis included studies which directly compared the efficacy of CDDP vs. C225 given concurrently with RT as definitive treatment of p16-positive and locally advanced/unresectable OPC. Primary endpoints included 2-year overall survival (OS) (death from any cause) and 2-year locoregional recurrence (LRR) (recurrence at primary site and/or regional lymph nodes), analysed separately. Six studies were included in the final analysis, including a total of 526 patients (range 18-205).
2-year OS. There were 313 patients in the CDDP + RT group and 113 patients in the C225 + RT group. The pooled odds ratio (OR), calculated for CDDP + RT vs. C225 + RT, was 0.35 (95% CI, 0.17-0.71; P = 0.003). 2-year LRR. There were 382 patients in the CDDP + RT group and 144 patients in the C225 + RT group. The pooled OR, calculated for CDDP + RT vs. C225 + RT, was 0.25 (95% CI, 0.15-0.45; P < 0.0001).
According to our results, patients receiving CDDP with irradiation had 2.9 and 4-fold decreased risk for death from any cause and locoregional recurrence, respectively. Further investigations are needed in order to determine the optimal treatment modalities in both p16-positive and negative OPC. Until then, CDDP-based chemoradiotherapy should be considered as first line therapy option and standard of care in p16-positive and locally advanced/unresectable OPC.
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All authors have declared no conflicts of interest.