Diagnostic utility of high‐risk HPV polymerase chain reaction–based testing in head and neck FNA specimens with indeterminate cytomorphology
Vanda F. Torous, William C. FaquinAbstract
Background
Fine‐needle aspiration (FNA) is critical in the initial diagnosis of many high‐risk human papillomavirus (HR‐HPV)–associated, metastatic oropharyngeal squamous cell carcinomas. Updated guidelines recommend HR‐HPV–specific polymerase chain reaction (PCR) analysis over p16 immunohistochemistry on FNA specimens because p16 performs poorly on cytology material. PCR‐based assays on liquid cytology material have demonstrated excellent analytic performance; however, the diagnostic utility of a positive HR‐HPV PCR result in specimens with indeterminate cytomorphology remains uncharacterized.
Methods
The authors retrospectively identified 279 head and neck FNA specimens that had paired HR‐HPV PCR testing on residual liquid cytology material over a 5‐year period. The positive predictive value for histopathologically confirmed squamous cell carcinoma on surgical follow‐up was calculated within each cytologic interpretive category.
Results
The HR‐HPV PCR results were positive in 50.2% of specimens, negative in 40.9%, and indeterminate in 9.0%. The HR‐HPV positivity rate ranged from 0% in specimens categorized as negative for malignancy to 57.3% in cytologically positive specimens, with 19.0%, 41.2%, and 50.0% positivity in the atypical, suspicious, and nondiagnostic categories, respectively. Among cytologically indeterminate specimens with positive HR‐HPV PCR results ( n = 14), the positive predictive value was 100% (95% confidence interval, 78.5%–100.0%). Blinded slide review additionally identified 15 cytologically positive specimens in which the definitive malignant interpretation depended substantially on HR‐HPV positivity; all 15 were confirmed as squamous cell carcinoma.
Conclusions
A positive HR‐HPV PCR result on liquid cytology material carries a positive predictive value of 100% for malignancy in cytologically indeterminate head and neck FNA specimens. These findings support integrating HR‐HPV PCR analysis into routine cytologic interpretation with the potential to upgrade some indeterminate specimens to malignant when HR‐HPV is detected, expediting definitive treatment and sparing patients additional, invasive sampling.