Human papillomavirus and cystic node metastasis in oropharyngeal cancer and cancer of unknown primary origin.

Toshimichi Yasui,Hidenori Inohara,Yoshifumi Yamamoto,Tadashi Yoshii,Susumu Nakahara,Eiichi Morii,Takeshi Todo,Yukinori Takenaka,Craig Meyers

doi:10.1371/journal.pone.0095364

Abstract

The clinical significance of human papillomavirus (HPV) in neck node metastasis from cancer of unknown primary (CUP) is not well established. We aimed to address the relationship of HPV status between node metastasis and the primary tumor, and also the relevance of HPV status regarding radiographically detected cystic node metastasis in head and neck squamous cell carcinoma (HNSCC) and CUP. HPV DNA was examined in 68 matched pairs of node metastasis and primary tumor, and in node metastasis from 27 CUPs. In surgically treated CUPs, p16 was examined immunohistochemically. When tonsillectomy proved occult tonsillar cancer in CUP, HPV DNA and p16 were also examined in the occult primary. Cystic node metastasis on contrast-enhanced computed tomography scans was correlated with the primary site and HPV status in another series of 255 HNSCCs and CUPs with known HPV status. Node metastasis was HPV-positive in 19/37 (51%) oropharyngeal SCCs (OPSCCs) and 10/27 (37%) CUPs, but not in non-OPSCCs. Fluid was collected from cystic node metastasis using fine needle aspiration in two OPSCCs and one CUP, and all fluid collections were HPV-positive. HPV status, including the presence of HPV DNA, genotype, and physical status, as well as the expression pattern of p16 were consistent between node metastasis and primary or occult primary tumor. Occult tonsillar cancer was found more frequently in p16-positive CUP than in p16-negative CUP (odds ratio (OR), 39.0; 95% confidence interval (CI), 1.4–377.8; P = 0.02). Radiographically, cystic node metastasis was specific to OPSCC and CUP, and was associated with HPV positivity relative to necrotic or solid node metastasis (OR, 6.2; 95% CI, 1.2–45.7; P = 0.03). In conclusion, HPV status remains unchanged after metastasis. The occult primary of HPV-positive CUP is most probably localized in the oropharynx. HPV status determined from fine needle aspirates facilitates the diagnosis of cystic node metastasis.

Highlights

Cervical lymph node metastasis from cancer of unknown primary (CUP) is a rare clinical entity and currently accounts for no more than 3% of head and neck squamous cell carcinoma (HNSCC) [1]
We have shown that human papillomavirus (HPV)-positive node metastasis is specific to oropharyngeal SCCs (OPSCCs), especially when OPSCC arises in the palatine tonsil and the base of the tongue
We demonstrated that HPV status, including the presence of HPV DNA, genotype, and physical status, was consistent between the primary tumor and its corresponding node metastasis

Summary

Introduction

Cervical lymph node metastasis from cancer of unknown primary (CUP) is a rare clinical entity and currently accounts for no more than 3% of head and neck squamous cell carcinoma (HNSCC) [1]. In many cases following its initial presentation as CUP, the primary site is unveiled predominantly in the oropharynx, in the palatine tonsil and the base of the tongue [2]. HPV prevalence in node metastasis from HNSCC has been well studied; it has been shown that HPV-positive node metastasis is specific to OPSCC [5,6], whereas the relationship of HPV status between the primary tumor and its corresponding node metastasis is not well established. HPV prevalence in node metastasis from CUP has been reported to vary from 28 to 92%, depending on the definition of CUP [8,9,10,11], whereas the relationship of HPV status between the node metastasis and its corresponding occult primary tumor has not been established

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