Prognosis of p16 and human papillomavirus discordant oropharyngeal cancers and the exploration of using natural language processing to analyze free-text pathology reports Journal Article


Authors: Shin, E.; Choi, J.; Hung, T. K. W.; Poon, C.; Riaz, N.; Yu, Y.; Kang, J. J.
Article Title: Prognosis of p16 and human papillomavirus discordant oropharyngeal cancers and the exploration of using natural language processing to analyze free-text pathology reports
Abstract: PURPOSETreatment deintensification for human papillomavirus-positive (HPV+)-associated oropharyngeal cancer (OPC) has been the catalyst of experts worldwide. In situ hybridization is optimal to identify HPV+ OPC, but immunohistochemistry for its surrogate p16INK4a (p16) is standard-of-care given its availability and sensitivity. HPV testing is not required for clinical management, so treatments are often administered on the basis of p16 status alone. However, the prognosis of p16/HPV discordant tumors is uncertain.MATERIALS AND METHODSThis cohort study included 727 consecutive patients with OPC with digitized unstructured pathology reports receiving curative radiation therapy at an academic cancer center. Natural language processing (NLP) methods were used to classify biomarker status and compared against manually derived classification. Patients were excluded if either p16 or HPV testing was not performed or equivocal. Primary end points were progression-free survival (PFS), cancer-specific survival (CSS), and overall survival.RESULTSNLP classified p16 and HPV status from a majority (91%) of reports. Accuracy, positive predictive value, sensitivity, and F-score for NLP-derived p16/HPV were 84%/82%, 91%/87%, 90%/89%, and 90%/88%, respectively. Four groups were identified: p16-positive (p16+)/HPV+ (75%), p16+/HPV-negative (HPV-; 13%), p16-negative (p16-)/HPV- (10%), and p16-/HPV+ (2%). There was no statistically significant difference in outcomes between p16+/HPV- and p16-/HPV- patients (5-year PFS 76.1% v 68.9%; P = .12; 5-year CSS 81.5% v 84.9%; P = .22). Number needed to harm calculations estimated one excess cancer-related death for every 10 p16+/HPV- patients, compared with that expected with p16+/HPV+ patients.CONCLUSIONNLP classified head and neck cancer pathology reports with high concordance with gold-standard categorization, but a conspicuous portion of reports could not be interpreted. p16/HPV discordant OPC constitutes a noteworthy minority of patients. The inferior prognosis of p16+/HPV- suggests that p16 alone for prognostication is insufficient-especially when considering treatment de-escalation.
Keywords: survival; outcomes; squamous-cell carcinoma; p16(ink4a); messenger-rna; head; neck cancers; subset; hpv dna; double positivity
Journal Title: JCO Clinical Cancer Informatics
Volume: 9
ISSN: 2473-4276
Publisher: American Society of Clinical Oncology  
Date Published: 2025-03-01
Start Page: e2400177
Language: English
ACCESSION: WOS:001425428800001
DOI: 10.1200/cci-24-00177
PROVIDER: wos
PUBMED: 39965177
Notes: Article -- e2400177 -- Source: Wos
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  1. Nadeem Riaz
    418 Riaz
  2. Yao Yu
    115 Yu
  3. Tony K.W. Hung
    32 Hung
  4. Chester Poon
    6 Poon