Abstract
The purpose of this study was to test whether the 8th edition of the AJCC/UICC TNM staging system (UICC) precisely differentiates between stages and reflects disease outcome in human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). OPSCC patients that were diagnosed between 2000 and 2016 were included in this analysis and HPV status was determined by combined DNA and p16 testing. Stratification was done according to 7th and 8th UICC staging rules. Incidence trends of HPV-associated tumorigenesis, 5-year overall survival (OS) according to tumor stages as well as the influence of therapy and prognostic factors toward the outcome were calculated using Kaplan-Meier method and Cox proportional-hazards model. A significant increase [2000; n = 8/39 (21%)-2015; n = 17/32 (53%); p = 0.002] in HPV-associated OPSCC was seen in the observation period. Together, 150/599 (25.0%) of the patients had HPV-driven OPSCC and 64.7% of curative treatments in all OPSCC patients included upfront surgery of the primary and the neck. 7th edition staging rules led to no discrimination in all respective four UICC stages in HPV OPSCC underlining the need for new staging rules. However, only discrimination between stages I vs. II and III vs. IV was significant in our patients with HPV-OPSCC (94.4 vs. 77.5%; p = 0.031 and 63.9 vs. 25.0%; p = 0.013), and stages II vs. III did not differ in OS rates (p = 0.257), when applying the new staging rules. For HPV-negative OPSCC, significant outcome differences were only seen between UICC stages III vs. IV (57.6 vs. 35.2%; p = 0.012). While the 7th edition of UICC shows invalid discrimination between stages, the 8th edition is more suitable for HPV-associated carcinoma. Due to lack of differentiation between stages II and III further adaption is essential.
Highlights
Rising incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) in several geographical areas have been reported over the last decades [1,2,3]
human papilloma virus (HPV) status was further assessed according to biometric data and patient possible prognostic factors for OPSCC (Table 1)
In further studies by our group, T-status in patients with HPV-associated OPSCC, performance status, N-category, and age in patients with HPV-negative OPSCC were identified in a RPA model to be important predictors for prolonged Overall survival (OS) after SRT [32], whereas we found that the model, introduced by Ang et al, seems to be unsuited for unselected, primary surgically treated patients [8]
Summary
Rising incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) in several geographical areas have been reported over the last decades [1,2,3]. After pooled analysis of 8 multinational studies with 5,642 patients with head and neck cancer and 6,069 controls, the risk of developing OPSCC was attributed with more lifetime sexual partners, more lifetime oral sex partners, and an earlier age at first sexual intercourse [4]. This rising incidence is in contrast to alcohol and tobacco-related head and neck cancers, which has remained constant or is in decline [5]. Retrospective and prospective studies show that patients suffering from HPVrelated OPSCC have advanced N-status compared to patients with HPV-negative OPSCC and contrary to that, significantly better local–regional control and survival after therapy [8,9,10]
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