Comprehensive management of HPV‐related squamous cell carcinoma of the head and neck of unknown primary

Abstract

Background Human papillomavirus (HPV)‐related squamous cell carcinoma of unknown primary (SCCUP) is currently rising in incidence but lacks a validated management approach. Aims This paper reviews the clinical presentation, diagnosis, and treatment of HPV‐related SCCUP. Materials and Methods The Medline/Pubmed database was searched by using the following keywords “CUP”, “cancer of unknown primary”, “HPV”, “human papilloma virus”, and “head and neck”. The references of the publications of interest were also screened for relevant papers. Results The clinical assessment of HPV‐related SCCUP includes a complete clinical examination, an endoscopic evaluation with white‐light and narrow band imaging, and radiologic assessment using morphologic and metabolic imaging. If the diagnosis remains unconfirmed, endoscopic examination under anesthesia with tonsillectomy ± base of tongue mucosectomy is performed. The therapeutic rationale aims to eradicate the involved lymph nodes and potential primary tumor with a sequence of chemoradiotherapy and neck dissection. Discussion As a general approach, p16‐negative SCCUP are truly HPV negative, whereas p16‐positive specimens require confirmation with HPV in situ hybridization or polymerase chain reaction to confirm HPV infection. If a cervical metastasis is considered HPV positive, the primary lesion is likely in the oropharynx, and further diagnostic interventions such as tonsillectomy seems to be mandatory. Whether the optimal treatment is neck dissection followed by adjuvant radiotherapy or concomitant chemoradiotherapy (CRT) (in case of extranodal extension or advanced lymph node stages) or definitive CRT followed by neck dissection (in case of positive 18F‐FDG‐PET/CT) remains a matter of debate. Solid scientific evidence supporting treatment de‐escalation in HPV‐related SCCUP is lacking, and the results of ongoing trials are at the brink of reporting. Conclusion Currently, the treatment of patients with HPV‐related SCCUP should not differ from the standard treatment of other SCCUP patients and is similarly based on the staging of the disease and general condition of the patient.

Carcinoma of Unknown Primary and the 8th Edition TNM Classification for Head and Neck Cancer

“…The improvement in the prognostic significance of TNM Classification of Malignant Tumors 8th edition should drive the discussion about changes in treatment modalities for p16+ HNCUP. Despite multiple studies having underlined the benefit of p16+ for OS, therapy regimens do not differ between p16+ and p16− HNCUP patients 21,33,34 . Recent studies have tried to reduce patient side effects by reducing treatment intensity 35–38 .…”

Technical feasibility of radiomics signature analyses for improving detection of occult tonsillar cancer

“…In previous studies, SCC was the most common histologic type, accounting for 78% of cases. However, the treatment strategies have been controversial, until now 6,8,9 . Although radiation therapy with or without neck dissection, including irradiation of all potential mucosal disease sites, has been effective, it causes substantial morbidity and side effects 6,14 .…”

Immune Infiltrates of m6A RNA Methylation-Related lncRNAs and Identification of PD-L1 in Patients With Primary Head and Neck Squamous Cell Carcinoma

“…HNSCC can arise from the mucosal linings of several anatomical sites including the larynx, hypopharynx, nasopharynx, and oropharynx and has unpredictable, high levels of heterogeneity ( Leemans et al, 2018 ). Although the carcinogenesis of HNSCC is not fully understood, tobacco use, excessive alcohol consumption, and human papillomavirus (HPV) infection are generally considered risk factors, especially for HNSCC arising in the oropharynx ( Rassy et al, 2019 ). Conventional treatment for HNSCC includes surgery, chemotherapy, and radiotherapy, but these result in a low curative rate of approximately 50% and a high recurrence rate.…”