Diagnostic Accuracy of FNA to Determine HPV Status in HPV-Associated Oropharyngeal Squamous Cell Carcinoma

Abstract

<h3>Purpose/Objective(s)</h3> Accurate diagnosis of human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) changes prognosis and can alter the treatment plan. Biopsy with fine needle aspiration (FNA) of cervical adenopathy is often performed during initial workup for OPSCC patients. FNA is limited by the amount of tissue obtained via small needle diameter and frequently requires repeat biopsies to determine HPV status. We evaluated the diagnostic accuracy of FNA biopsies to determine HPV status. <h3>Materials/Methods</h3> Consecutive patients with known HPV-associated OPSCC at a single institution between 2015 and 2021 were retrospectively analyzed. Demographic, clinical, and pathologic details were extracted from the electronic medical record for descriptive statistics. Patients with lymph node metastases undergoing initial biopsy with FNA were included. Pathology samples underwent central review and immunohistochemistry staining for p16 was used as a surrogate marker for HPV status. <h3>Results</h3> Two hundred ninety new cases of OPSCC were evaluated. FNA of lymph node metastases was the initial diagnostic procedure in 153 (52.8%) patients with median age at diagnosis of 57.0 (range 31.7 – 82.0). The population was mostly male (90.2%) with tumors most commonly located in the base of tongue (45.1%) and tonsil (42.5%). Initial FNA was positive for malignancy in 115/153 (75.2%) patients and non-diagnostic in 38/153 (24.8%). P16 staining on diagnostic FNA showed: 54/115 (47.0%) p16 positive, 6/115 (5.2%) p16 negative, 55/115 (47.8%) p16 indeterminate. In patients without a diagnosis of malignancy or p16 indeterminate, repeat FNA was performed in 30/93 (32.3%) patients. Of the repeat FNA patients: 7/30 (23.3%) remained non-diagnostic for malignancy, 16/30 (53.3%) p16 positive, 7/30 (23.3%) p16 indeterminate. In summary, 93/153 (60.8%) patients undergoing initial FNA and 14/30 (46.7%) undergoing repeat FNA were non-diagnostic of malignancy or p16 indeterminate. The final yield of FNA biopsies to determine malignancy status or p16 status was 76/153 (49.7%). <h3>Conclusion</h3> HPV-associated OPSCC patients undergoing FNA for initial diagnosis frequently are not diagnostic for malignancy or are indeterminate for p16 status, requiring repeat FNA or biopsy of the primary site. This can potentially cause treatment delay and increase morbidity and cost to the patient.