How cytology and cytology-based HPV testing could assist clinicians in the diagnosis of head and neck squamous cell carcinoma

Abstract

Introduction: Given the limitations of biopsy in the diagnosis of head and neck squamous cell carcinoma (HNSCC), we explored the diagnostic efficiency of cytology at the primary tumor site of HNSCC. In addition, p16 immunohistochemistry (IHC) can yield a false positive result in the detection of HPV status in HNSCC, so we sought to perform APTIMA HPV testing to improve the diagnostic accuracy for HPV status in HNSCC patients. Methods We categorized 151 enrolled HNSCC patients into two groups. The first cohort comprised 78 patients who underwent cytology examination at the primary tumor sites of HNSCC. The other cohort consisted of 132 patients whose HPV status was evaluated and whose cytology specimens underwent HPV APTIMA testing while their histologic biopsy specimens underwent p16 IHC. Patients with discordant Aptima HPV and p16 IHC results were reexamined with RNAscope assays. Results Among the 78 patients whose samples from the primary site of HNSCC underwent cytological examination, 71 underwent simultaneous pathological biopsy; due to sampling difficulties, the biopsy failed for the remaining 7 patients. There were 13 cases of HNSCC that could not be definitively diagnosed as SCC with preoperative biopsy. Of these 13 histologically underdiagnosed cases, SCC was ultimately diagnosed cytologically in six cases. Of the 7 patients whose preoperative biopsy failed, five were cytologically diagnosed with SCC. For all 132 HNSCC patients whose cytology specimens underwent HPV APTIMA testing, compared to p16 IHC, the APTIMA HPV test had greater specificity and positive predictive values (98.8% and 98.0% vs. 89.2% and 84.5%, p2 = 0.018, p3 = 0.020) and similar sensitivity and negative predictive values (98.0% and 98.8% vs. 100% and 100%, p1 = 1.000, p4 = 1.000). Conclusion Cytological examination can complement preoperative pathological biopsy in the diagnosis of HNSCC at the primary tumor site. Furthermore, cytology specimens could be utilized for HPV testing using the APTIMA HPV test to uncover potential errors in p16 IHC results on biopsy samples, allowing a more precise diagnosis and treatment of HNSCC.