Development of a Novel Composite Pathologic Risk Stratification for Surgically Resected HPV-Associated Oropharyngeal Cancer

Development of a Novel Composite Pathologic Risk Stratification for Surgically Resected HPV-Associated Oropharyngeal Cancer: This retrospective cohort study assesses the performance of the traditional pathologic risk stratification system for surgically resected human papillomavirus–associated oropharyngeal squamous cell carcinoma and proposes an alternate composite risk stratification system.






John D. Cramer, MD1; Yusuf Dundar, MD1; Jeffrey Hotaling, MD1; et alS. Naweed Raza, MD1; Ho-Sheng Lin, MD1

Author Affiliations

1Department Otolaryngology–Head and Neck Surgery, Wayne State University School of Medicine, Detroit, Michigan

JAMA Otolaryngol Head Neck Surg. 2019;145(12):1105-1114. doi:10.1001/jamaoto.2019.0820



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Key Points

Question  How does pathologic risk stratification perform in surgically resected human papillomavirus–associated (HPV+) oropharyngeal cancer (OPSCC) and HPV-unassociated head and neck squamous cell carcinoma (HNSCC)?



Findings  In this retrospective cohort study of 15 324 patients, traditional pathologic risk stratification had poor survival discrimination in patients with HPV+ OPSCC. A novel composite pathologic risk stratification system was developed for HPV+ OPSCC that was associated with improved survival discrimination.



Meaning  Pathologic adverse features carry different prognostic importance in HPV+ OPSCC than in HPV-unassociated HNSCC. The pathologic risk stratification system used for HPV+ OPSCC after definitive surgery is in need of refinement.



Abstract

Importance  Human papillomavirus–associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is a distinct form of head and neck squamous cell carcinoma (HNSCC) with its own American Joint Committee on Cancer staging system. However, pathologic risk stratification for HPV+ OPSCC largely remains based on the experience with HPV-unassociated HNSCC.



Objective  To compare the survival discrimination of traditional pathologic risk stratification for both HPV+ OPSCC and HPV-unassociated HNSCC and derive a novel pathologic risk stratification system for HPV+ OPSCC with improved survival discrimination.



Design, Setting, and Participants  In this retrospective cohort study, we used the National Cancer Database to identify 15 324 patients diagnosed with nonmetastatic HNSCC between January 1, 2010, and December 31, 2013, who were treated with upfront surgery and neck dissection. We compared traditional pathologic risk stratification for HPV+ OPSCC and HPV-unassociated HNSCC and then derived a novel pathologic risk stratification system. Analyses were performed from July 1, 2018, to January 31, 2019.



Exposures  Definitive primary surgical resection and neck dissection.



Main Outcomes and Measures  Survival discrimination of pathologic risk stratification systems measured with concordance indices.



Results  This retrospective cohort study included 15 324 patients (10 779 men and 4545 women; mean [SD] age, 59.9 [11.8] years) with surgically treated nonmetastatic HNSCC. Separation of survival curves for HPV-unassociated HNSCC using traditional pathologic risk stratification (5-year overall survival for the low-, intermediate-, and high-risk groups) were 76.2%, 54.5%, and 40.9%, respectively. Separation curves for HPV+ OPSCC were 93.2%, 88.9%, and 83.7%, respectively. Human papillomavirus–unassociated HNSCC had a concordance index of 0.68, whereas HPV+ OPSCC had a concordance index of 0.58. A novel risk stratification system for HPV+ OPSCC that more closely fits actual survival rates for HPV+ OPSCC was derived. The system incorporated the composite number of pathologic adverse features. This composite risk stratification system was associated with an improved concordance index of 0.67 for HPV+ OPSCC. Adjuvant treatment with radiation was not associated with improved survival for patients categorized as low risk according to the new risk stratification system, but this treatment was associated with improved survival for patients in the intermediate- and high-risk groups.



Conclusions and Relevance  Traditional pathologic risk stratification shows poor survival discrimination for HPV+ OPSCC and classifies many patients with an excellent prognosis as high risk. We derived a novel composite pathologic risk stratification system for HPV+ OPSCC that may be associated with improved survival discrimination.