HPV and Oropharyngeal Cancer in the Eighth Edition of the TNM Classification: Pitfalls in Practice

This review is a call for mindfulness and precision when applying TNM 8 in oropharyngeal cancers. Implications, intentions, and weaknesses of TNM 8 are addressed in light of our own investigations and the published literature. In TNM 8, the impact of p16(INK4A) status on the staging of oropharyngeal SCC highlights i) that underlying evidence is scarce, ii) its stage grouping exclusively has prognostic intention, and iii) that a noncritical application of TNM 8 might negatively impact the patients' survival as the perception of TNM 8 as having therapeutic intention may lead to de-escalating treatment regimens in p16(INK4A)-positive cases, specifically when grouped into stage I despite the presence of neck metastasis. If other parameters from HPV positivity that also have a negative impact on the patient's survival, such as smoking or the presence of comorbidity, are neglected in therapy planning, survival outcomes might even become worse. Future studies applying TNM 8 and further investigating the value of p16(INK4A) as surrogate marker for active HPV infections will identify whether or not changes in TNM 8 should have therapeutic implications in HPV-associated, only p16(INK4A)-positive cases or whether this impact additionally holds true for nontonsillar cancers.