A Middle-Aged Man With a Unilateral Neck Mass: What’s the Next Step?

Chethan Ramamurthy, MD, and Ronald Rubin, MD—Series Editor

A 45-year-old man presented to the office of a primary care provider (PCP) with a 2-month history of a noticeable lump in his right neck. He was a nonsmoker and recently had been treated with a course of amoxicillin-clavulanate for a dental abscess.

He had first noticed the lump 2 months ago and had been seen by his PCP, who recommended following him expectantly in light of the recent upper respiratory tract infection symptoms he had reported at the time. He then had been seen for a routine dental checkup and had been prescribed a 1-week course of amoxicillin-clavulanate for some erythema noted along his right gingiva, which the dentist believed was related to the neck mass. Nevertheless, the mass persisted.

Physical examination of the man’s neck revealed a normal thyroid, but a 2-cm, firm lymph node in the right anterior cervical chain. No supraclavicular, posterior cervical, or left-sided adenopathy was appreciated.

The results of a complete blood count with differential and a comprehensive metabolic panel were normal. Results of an HIV test were negative.

Which of the following is the next best step in management?

A. A course of levofloxacin-metronidazole.
B. Computed tomography (CT) scan of the head and neck, followed by fine-needle aspiration of the mass.
C. Excisional biopsy of the mass.
D. Referral to an infectious disease specialist for tuberculosis testing.

Answer: B. CT scan of the head and neck, followed by fine-needle aspiration of the mass.

The case presented here is a typical presentation of human papillomavirus–associated oropharyngeal squamous cell cancer (HPV OPSCC), which is a growing concern. HPV OPSCC now represents greater than 70% of all OPSCC cases, while before 2000, only 40% of OPSCC cases were HPV-related.1 The different biology of HPV OPSCC has in turn led to a changing demographic. While traditional head and neck squamous cell cancer (HNSCC) is seen primarily in older smokers, HPV OPSCC is seen more commonly in middle-aged male nonsmokers, with oral sex being the primary risk factor.2

Among HPV OPSCC cases, nearly 90% are associated with HPV 16. Widely known as one of the HPV strains causing cervical cancer, it also has a central epidemiologic role in OPSCC. Importantly, the available vaccines against HPV both cover HPV 16 and have been demonstrated to be effective against oral HPV infection.2

Clinical Presentation and Diagnosis

The importance of recognizing HPV OPSCC is underscored by its insidious, subtle presentation. Because the most common sites for HPV OPSCC are the base of tongue and the palatine tonsils, primary lesions often are not noticed until metastasis to the cervical lymph nodes has occurred. 

As opposed to HNSCC, which more commonly presents with more easily noticeable symptoms such as weight loss, sore throat, dysphagia, and odynophagia, the primary presenting symptom of HPV OPSCC is a neck mass.3 This can be incorrectly attributed to an infectious etiology (thus, Answers A and D are incorrect), an inflammatory etiology, or an endocrinologic etiology, often delaying diagnosis.

When OPSCC is suspected, CT of the head and neck usually is the best first step in management (Answer B, then, is the correct choice). Imaging can help identify the primary lesion and define metastatic spread and its relation to important neck anatomy. 

Fine-needle aspiration of a unilateral neck mass usually is sufficient to establish a tissue diagnosis, with a sensitivity of 88% and specificity of 100%, making core needle and excisional biopsy (Answer C) unnecessary in most cases.1 As such, much of the preliminary diagnostic workup can be accomplished in the primary care setting.

Prognosis and Treatment: The Silver Lining

While the rising incidence of HPV OPSCC is troubling, evidence suggests that this entity has a superior prognosis to HPV-negative OPSCC.4 The improved survival of patients with HPV OPSCC makes reducing long-term iatrogenic morbidity an important consideration when selecting therapy.

The traditional treatment regimens for OPSCC involve some combination of radiation, surgery, and platinum-based chemotherapy with the attendant pain, scarring, xerostomia, speech and swallowing dysfunction, neurotoxicity, and nephrotoxicity. Several recent de-escalation trials have shown promising results when reducing the radiation dose, replacing platinum agents with less-toxic monoclonal antibodies, or utilizing minimally invasive surgical techniques.5 These studies suggest that with appropriate patient selection and establishment of reduced-intensity treatment regimens, many of the growing number of patients with HPV OPSCC may achieve excellent survival with less long-term toxicity.

Outcome of the Case

The patient underwent CT of the neck and fine-needle aspiration of his neck mass, which demonstrated stage 3 disease with a small primary lesion at the base of the tongue. He underwent concurrent chemotherapy and radiation therapy and had a complete clinical response; his case is now being followed expectantly.

Chethan Ramamurthy, MD, is a fellow in hematology/oncology at the Temple Health Fox Chase Cancer Center in Philadelphia, Pennsylvania.

Ronald Rubin, MD, is a professor of medicine at the Temple University School of Medicine and is chief of clinical hematology in the Department of Medicine at Temple University Hospital, both in Philadelphia, Pennsylvania.


  1. Moore KA II, Mehta V. The growing epidemic of HPV-positive oropharyngeal carcinoma: a clinical review for primary care providers. J Am Board Fam Med. 2015;28(4):498-503.
  2. Young D, Xiao CC, Murphy B, Moore M, Fakhry C, Day TA. Increase in head and neck cancer in younger patients due to human papillomavirus (HPV). Oral Oncol. 2015;51(8):727-730.
  3. McIlwain WR, Sood AJ, Nguyen SA, Day TA. Initial symptoms in patients with HPV-positive and HPV-negative oropharyngeal cancer. JAMA Otolaryngol Head Neck Surg. 2014;140(5):441-447.
  4. Lewis A, Kang R, Levine A, Maghami E. The new face of head and neck cancer: the HPV epidemic. Oncology (Williston Park). 2015;29(9):616-626.
  5. Masterson L, Moualed D, Liu ZW, et al. De-escalation treatment protocols for human papillomavirus-associated oropharyngeal squamous cell carcinoma: a systematic review and meta-analysis of current clinical trials. Eur J Cancer. 2014;50(15):2636-2648.