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Introduction

In the last decade, the relationship between HPV status and oropharyngeal squamous cell carcinoma (OPSCC) has been thoroughly investigated . Multiple studies have demonstrated that HPV-positive OPSCC generally affects younger Caucasian males more frequently . Further, HPV-positive oropharyngeal cancer does not appear to be associated with severity of alcohol consumption and tobacco smoking . These findings implicate HPV OPSCC as a separate clinical entity than its HPV-negative counterpart, and expand the “at risk” group to a broader subset of otherwise healthy individuals.

Over the years, many investigators have studied the lymphatic drainage patterns of head and neck cancer. In the 1930s, Rouvière determined that lymphatic drainage patterns of squamous cell carcinomas correspond with anatomic subsite . Since Rouvière’s initial investigations, several others have studied the lymphatic drainage patterns of the oropharynx to determine the topographical incidence of cervical nodal disease according to tumor site and size . In 1972, using clinically positive nodes (> 1 cm) to indicate lymphatic spread, Lindberg calculated the incidence of cervical lymph node disease, nodal multiplicity, and contralateral cervical lymph node disease with regard to oropharyngeal subsite and tumor size . Although historically important, his study is limited by a lack of HPV status distinction and may not be applicable to HPV-positive patients. Since Lindberg’s initial studies, many have investigated the risk of occult lymph node metastasis in an effort to determine the necessity of elective neck dissection or radiation therapy in the clinically N0 neck . These studies, however, are also limited by the lack of HPV status distinction.

As the incidence of HPV-positive OPSCC has increased in the decade, recent studies have not only revealed epidemiologic differences, but also demonstrated distinct histopathological and morphological differences between HPV-positive and HPV-negative tumors . It has been recently demonstrated that HPV-positive tumors exhibit basaloid and poorly differentiated histopathologic characteristics, distinctly different than the keratinizing characteristics of HPV-negative tumors . Further studies have revealed distinct radiological features of tumor and nodal characteristics between HPV statuses . For example, HPV-positive tumors are more likely to demonstrate exophytic well-defined borders, whereas HPV-negative tumors are likely to demonstrate invasion of adjacent muscle . In addition, well-defined cystic metastases are suggested to be associated with HPV-positivity .

These distinct histopathologic and morphologic features are suggestive of distinct tumor behavior patterns and may correlate to distinct differences in nodal staging in patients presenting with HPV-positive oropharyngeal tumors. Shoushtari et al. is the only group to have previously investigated clinical nodal staging in HPV-positive patients, but their study is limited to T1 and T2 tonsil squamous cell carcinomas . Although it has been well documented that OPSCC has a 30-35% risk of cervical neck occult metastasis, to date, no one has thoroughly studied clinical nodal staging in all HPV-positive OPSCC subsites . The aim of our study is to evaluate clinically positive nodal disease in all subsites of HPV-positive OPSCC upon presentation. The importance of this research is based upon the fact that treatment, both surgical and non-surgical, is often influenced by cervical nodal disease. This study was based upon clinical staging that incorporated radiographic staging because initial treatment decisions are based upon the initial clinical stage. Knowing the relationship of nodal metastasis to clinical stage will alert the clinician (radiation oncologist and/or surgeon) to treat at risk areas.

In the era of HPV, we aim to revisit Lindberg’s analysis of clinical nodal incidence, with specific emphasis on oropharyngeal T-stage and primary tumor site and their associations with presence or absence of clinical neck disease (cN0), nodal multiplicity (cN2b), and bilateral and/or contralateral lymphadenopathy (cN2c).