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Cytopathology in focus: Direct HPV testing in FNAs from cervical lymph node metastases

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Swikrity U. Baskota, MD

May 2020—According to a Centers for Disease Control and Prevention study from 2008 to 2012, there are about 16,000 cases of HPV-positive oropharyngeal squamous cell carcinoma per year in the United States. These carcinomas tend to present with small primary lesion and early nodal metastases as an initial manifestation of the disease. Furthermore, carcinoma of unknown primary presenting as a cystic metastasis in the head and neck has been linked frequently to oropharyngeal squamous cell carcinomas, mainly of palatine tonsils and base of the tongue. Because it is easy to access these clinically evident neck masses, fine-needle aspiration cytology has been the cornerstone of the diagnoses of these lesions.

It is recommended that HPV-DNA testing be done in these FNA samples to identify the site of unknown primary and determine the HPV status of a metastatic node from a known oropharyngeal squamous cell carcinoma. Determining that an oropharyngeal squamous cell carcinoma is positive for high-risk HPV has significant implications for patient prognosis, and it is now integrated into the recently updated AJCC Cancer Staging Manual, eighth edition. HPV status also determines patient eligibility for clinical trials of new treatment regimens and modalities.

In recent years, several studies have been done to confirm high-risk HPV, using DNA/RNA-based in situ hybridization, polymerase chain reaction-based methods, or HPV L1 immunohistochemistry along with p16 immunohistochemistry. Recently there has been a paradigm shift to molecular testing of high-risk HPV DNA in liquid-based cytology fine-needle aspiration cytology specimens from the head and neck region using various platforms like Aptima, Cervista, Cobas, Hybrid Capture 2, and BD Onclarity. However, there are rare to no published studies that used the same HPV-testing platform in both the cytological and follow-up surgical specimens.

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