Head and Neck Cytopathology: Human Papillomavirus-Positive Carcinomas, Including Diagnostic Updates, Testing Modalities, and Recommendations
Section snippets
Overview to human papillomavirus-positive head and neck squamous cell carcinoma
Oropharyngeal squamous cell carcinoma (OPSCC) caused by transcriptionally active human papillomavirus (HPV) is now well established as a unique form of head and neck cancer.1, 2, 3, 4, 5 The 1980s saw the beginning of sharply differing incidences between the 2 leading pathways to head and neck cancer, with a significant increase in HPV-positive OPSCC and a contrasting decrease in conventional alcohol and tobacco–related head and neck squamous cell carcinoma (HNSCC). In the United States, the
Cytologic evaluation of human papillomavirus-positive head and neck squamous cell carcinoma
Metastatic head and neck carcinomas to cervical lymph nodes are frequently diagnosed by fine-needle aspiration (FNA), which is often done in conjunction with ultrasound guidance.15, 16, 17, 18 Even though HPV-positive OPSCC may occur as a relatively small primary lesion (low T stage) within the tonsillar crypts where it is difficult to detect except by tissue biopsy, it often presents with early cervical nodal metastases (high N stage). The frequent presentation as metastatic carcinoma has led
Histologic features of human papillomavirus-positive head and neck squamous cell carcinoma
When encountered in surgical pathology material, HPV-positive OPSCC also exhibits a characteristic histomorphologic appearance that departs from that of conventional HNSCC in many ways.21, 22, 23 Although conventional HNSCC typically arises from surface squamous dysplasia as cords and nests of keratinizing cells with an associated desmoplastic stromal reaction, HPV-positive OPSCC arises from the specialized oropharyngeal crypt epithelium as cohesive lobules and sheets of cells with little or no
Other forms of human papillomavirus-positive head and neck squamous cell carcinoma
As previously described, the prototypical HPV-positive HNSCC arises in the oropharynx, but there are other forms of HPV-positive head and neck carcinoma, including those that arise in the oropharynx and the sinonasal cavity. These other forms of HPV-positive carcinomas are less likely to be sampled by FNA but instead are typically detected by tissue biopsy. To date, only HPV-positive OPSCC and its SCC subtypes are strongly linked by evidence-based data to improved patient outcome relative to
The role of human papillomavirus testing in head and neck squamous cell carcinoma
Performing testing for HR-HPV in HNSCC is important for many reasons. Aside from its prominent role as a prognostic marker, determining HPV status can grant a patient eligibility for clinical trials investigating novel treatment options (eg, radiotherapy deescalation or vaccine-based therapies), and it is now integrated into the recently updated 8th Edition of the AJCC staging manual.12, 13 In addition, the site specificity of HPV-positive SCC can be exploited such that demonstrating HR-HPV in
Conventional methods for high-risk–human papillomavirus testing using formalin-fixed paraffin-embedded material
There are many methods available for HR-HPV testing in HNSCC, including p16 immunohistochemistry (IHC),47, 48, 49, 50 in situ hybridization (ISH) for HR-HPV DNA,51 polymerase chain reaction (PCR) for the E6 and E7 proteins,52, 53 ISH for the E6 and E7 messenger RNA (mRNA) transcripts,42, 54, 55 and combinations of these methodologies. These and other methods of testing for HR-HPV differ in their sensitivities, specificities, cost, technical requirements, and applicability to a diagnostic
High-risk–human papillomavirus testing applied to fine-needle aspiration samples of head and neck squamous cell carcinoma
Approximately 80% to 85% of HPV-positive OPSCCs present with early cervical nodal metastases, which can be easily sampled and diagnosed using FNA.9, 47 Cytologic evaluation has become an essential method for the early detection of metastatic HNSCC, and FNA biopsies can provide adequate material to determine HR-HPV status, leading to overall improved patient care. The current CAP Guideline recommends HR-HPV testing be performed on HNSCC FNA samples from all patients with known OPSCC not
Summary
In summary, the recent CAP Guideline provides recommendations for the effective performance and interpretation of HR-HPV testing in HNSCC. Among the 14 recommendations, one states that HR-HPV testing should be performed on FNA samples of metastatic HNSCC to cervical lymph nodes. Given the high frequency of metastasis to cervical lymph nodes by HPV-positive OPSCCs, FNA represents a simple and effective method to sample and diagnose these cancers. There is a wide range of options for HR-HPV
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