Prognostic Impact of AJCC/UICC 8th Edition New Staging Rules in Oropharyngeal Squamous Cell Carcinoma

Abstract

IntroductionThe 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).Patients and methodsOPSCC 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.ResultsA 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).DiscussionWhile 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.

Comparison of contemporary staging systems for oropharynx cancer in a surgically treated multi‐institutional cohort

“…They concluded that the 8th edition is more suitable for Japanese HPV− OPSCC patients. A similar study with a mixed cohort from Germany ( n = 561) came to the opposite conclusion, indicating a better prognostic stage discrimination of the 8th edition for HPV+ OPSCC, which is in line with our findings.…”

“…However, smoking, alcohol consumption and sexual habits and prevalence rates of HPV associated and non‐HPV associated OPSCC are strongly dependent on geography. Even among developed countries, these rates vary substantially . Therefore, the prognostic stratification power of a staging system developed in a population may vary elsewhere .…”

Long‐term analysis of transorally resected p16 + Oropharynx cancer: Outcomes and prognostic factors

“…The AJCC 7th edition pN‐category and TNM‐grouping were not prognostic in our previous report, whereas the AJCC 8th edition pathologic tumor, nodal, and TNM‐staging are associated with DFS and DSS in the current study. The AJCC 8th edition staging has been shown to improve hazard discrimination and outcome prediction for HPV + OPSCC in several studies, and the current study provides further validation; however, as expected from larger multicenter studies, the absolute number of pN2 cases is limited. Angioinvasion was prognostic for DSS, whereas perineural invasion, routinely reported ECS (present/absent), and routinely reported soft tissue metastasis (STM) (present/absent) were not associated with reduced DFS or DSS, similar to the thesis .…”

Pros and Cons of the New Edition of TNM Classification of Head and Neck Squamous Cell Carcinoma

“…Moreover, another retrospective evaluation did not report differences between stage I and stage II [30]. In a European cohort Würdemann et al [31] reported no difference in OS rates (p = 0.257) in stage II versus III when applying the new staging rules. For HPV-negative OP-SCC, significant outcome differences were only seen between UICC stages III and IV (57.6 vs. 35.2%; p = 0.012).…”

“…Similarly, those who were upstaged in pN classification presented a worse DFS (17.1 vs. 61.2%; p = 0.001) and OS (8.5% versus 37.9%; p < 0.001) [30]. Table 5 summarizes the controversial results of studies on the new TNM [9,10,28,[31][32][33][34].…”