Clinical Features of Human Papilloma Virus-Related Head and Neck Squamous Cell Carcinoma of an Unknown Primary Site

Abstract

Purpose: Head and neck squamous cell carcinoma of an unknown primary site (HNSCCUP) is a heterogeneous group of tumors that includes the human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma. To investigate the relationship between HNSCCUP and HPV, we reviewed p16 overexpression and HPV DNA in lymph node metastases and examined their correlation with the primary site and clinical features. Materials and Methods: Thirty-three patients with HNSCCUP were retrospectively studied. Dissected neck metastases were analyzed for p16 overexpression by immunohistochemistry, and the presence of HPV DNA was investigated by in situ hybridization. Results: Of the 33 patients, 8 (24%) exhibited p16 overexpression. p16-positive lymph node metastases contained significantly more HPV DNA and were most frequently associated with occult primary lesions in the oropharynx and a favorable prognosis. Patients with a lower alcohol consumption, only level II/III metastasis, and cystic lymph node metastasis tended to have p16 overexpression. Conclusions: This is the first report on the relationship of HNSCCUP with p16 and HPV DNA status in Asian patients. In total, 24% of the HNSCCUP patients were p16 positive. p16 overexpression in neck metastasis was predictive of both an occult primary lesion in the oropharynx and an association with HPV infection. Alcohol consumption, location, and features of neck metastasis were correlated with p16 expression.

Prognostic factors for head and neck cancer of unknown primary including the impact of human papilloma virus infection

“…One can even suggest that HNCUP could be considered a subtype of these cancers, since they are the most common occult primary, having cystic metastasis in the same area of the neck with similar age and prognostic panorama. The reported HPV prevalence for HNCUP differs widely in previous studies, between 22 and 91% [11, 12, 23, 24]. Larger studies are needed to better define the HPV prevalence and, it probably varies in different parts of the world and over time.…”

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

“…The traditional profile of a patient with SCCUP was that of a middle-aged (50-65 years) white men, with heavy smoking and alcohol abuse history. 6,16,17,20 The male predominance correlates with the ease of female-to-male HPV transmission which is precipitated by the high number of sexual partners and oral sex encounters. 6,16,17,20 The male predominance correlates with the ease of female-to-male HPV transmission which is precipitated by the high number of sexual partners and oral sex encounters.…”

“…6,16,17,20 The male predominance correlates with the ease of female-to-male HPV transmission which is precipitated by the high number of sexual partners and oral sex encounters. 16,17,19,20,[22][23][24] However, one retrospective analysis of a small series of patients showed that the HPV status does not correlate with neck stage at presentation. The clinical N classification at diagnosis is usually N2/N3 (11%-95%).…”

Radiologic Differences between Human Papillomavirus-Related and Human Papillomavirus-Unrelated Oropharyngeal Carcinoma on Diffusion-Weighted Imaging

“…The diagnostic potential and prognostic role of imaging biomarkers for HPV status in OPC remains unclear. Several previous studies have demonstrated differences between HPV+ and HPV- OPC using anatomic imaging techniques, including CT and MRI [10,11,12,13]. These distinguishing imaging features include a tendency for HPV+ OPC to present with smaller, well-defined primary tumors and cystic nodal metastases.…”