ABSTRACT
In the US, 60% to 80% of oropharyngeal squamous cell carcinomas (OPSCCs) are associated with human papillomavirus (HPV). However, until recently, no consensus existed about when and how to test for HPV in patients with head and neck cancers. We aimed to evaluate the use of p16 and HPV testing at our institution because p16 immunohistochemistry is reportedly a reliable surrogate marker for HPV detection in OPSCCs. METHODS: We identified all cases at our institution of primary or metastatic squamous cell carcinoma (SCC) of the head and neck with a concurrent p16 immunostain analysis from January 1, 2013, through August 31, 2018. Patient demographic data, tumor characteristics, p16 result, and any HPV result (in situ hybridization and E6 and E7 RNA test) were captured. RESULTS: We identified 104 patients. Most primary tumors (53/57 [93.0%]) and metastases (40/47 [85.1%]) were positive for p16. Thirty-seven cases (35.6%) had reflex high-risk HPV (HR HPV) testing performed. Of the 35 p16-positive cases, 6 had discrepant HR HPV results (p16+ /HPV- ). We identified 47 p16 immunostains that were performed on lymph nodes with primary tumors of unknown origin. Most were cytology cases (34/47 [72.3%]), and most were p16 positive (40/47 [85.1%]). Neither tumor differentiation nor tumor keratinization was predictive of p16 positivity. Tumors with basaloid differentiation were universally p16 positive. CONCLUSION: p16 immunohistochemistry accurately identifies HPV-positive OPSCC. Cytology specimens have an important role in characterizing SCC of unknown origin. HR HPV testing is not routinely required, and results may be discrepant with p16 findings.
Subject(s)
Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/virology , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Oropharyngeal Neoplasms/genetics , Oropharyngeal Neoplasms/virology , Aged , Aged, 80 and over , Alphapapillomavirus/genetics , Biomarkers, Tumor/genetics , Female , Human Papillomavirus DNA Tests/methods , Humans , Lymph Nodes/virology , Male , Middle Aged , Papillomavirus Infections/genetics , Papillomavirus Infections/virology , RNA, Viral/geneticsABSTRACT
INTRODUCTION: Indeterminate thyroid cytology (ITC) occurs in 20% to 25% of cases, and the associated risk of malignancy ranges from 5% to 30%. The genomic classifier ThyroSeq (CBLPath/UPMC, Rye Brook, NY), a targeted next-generation sequencing technology, could classify ITC nodules as malignant and nonmalignant. We sought to characterize our institutional experience with ThyroSeq testing. MATERIALS AND METHODS: We retrospectively identified all patients seen from January 2015 through November 2019 who had ITC nodules analyzed with ThyroSeq. Relevant clinical, pathologic, and resection data were reviewed. RESULTS: Of the 133 cases identified, diagnostic categories included atypia (or follicular lesion) of undetermined significance) (n = 65 [48.9%]), suspicious for follicular neoplasm (SFN) (n = 48 [36.1%]), and suspicious for Hürthle cell neoplasm (n = 20 [15.0%]). About half of the papillary thyroid carcinoma (PTC) cases (n = 9 [56.3%]) and more than one-third of the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) cases (n = 3/8 [37.5%]) were classified as SFN. Most patients (n = 87 [65.4%]) did not undergo resection; of these, 73 (83.9%) were negative for all molecular alterations. Of the 54 cases with molecular alterations, isolated RAS or RAS-like variants were most common (n = 35 [64.8%]); 9 (25.7%) were identified in PTC and 8 (22.9%) in NIFTP. NRAS was the most common alteration (n = 20 [37.0%]), followed by HRAS (n = 6 [11.1%]), which was mostly detected in NIFTP cases (n = 4 of 6 [66.7%]). CONCLUSION: Resection was avoided in 73 patients (54.9%) because of negative ThyroSeq results. ThyroSeq v2 and v3 offered a more accurate categorization of ITC nodules, improved patient management, and reduced unnecessary surgical procedures.
