Benjamin L. Judson, MD, MGA, provides additional insight on this topic. Click here for more.

In a recently published study from the Medical University of South Carolina, researchers conducted a retrospective review of medical records of patients who were diagnosed with oropharyngeal squamous cell carcinoma (OPSCC) and examined the symptomatic differences between patients who were human papillomavirus (HPV)-positive and HPV-negative. This study is the first of its kind that reports on the initial symptoms of OPSCC.

Although media attention has been given lately to HPV and its connection to cervical cancer, data are now also showing a link between oral HPV and OPSCC.1 Cases of HPV-positive OPSCC tumors have risen to 70% since 2009, up from 40.5% before 2000.1 However, OPSCC can be caused by other factors, including alcohol consumption and smoking, and people with OPSCC resulting from environmental influences such as those usually present with HPV-negative tumors. 

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RELATED: HPV-Associated Oropharyngeal Cancer: A Growing Dilemma

According to the review of medical records of patients with OPSCC diagnosed between January 1, 2008 and May 20, 2013, the most noticeable differences in patients with OPSCC were the initial symptoms. The data showed that 44% of patients felt a neck mass and 33% complained of a sore throat prior to diagnosis; however, these are symptoms that can result in diagnoses of other conditions. Patients who were HPV-positive initially noticed a neck mass more frequently than HPV-negative patients did (51% vs 18%; P=0.02), whereas HPV-negative patients were more likely to first experience a sore throat (53% vs 28%; P=0.09), difficulty swallowing (41% vs 10%; P=0.05), or painful swallowing (24% vs 6%; P=0.04).

As with many cancer types, early diagnosis of tumors is important to overall survival, although many patients do not visit a doctor until they experience more concerning symptoms. Therefore, the opportunity exists for the medical team to be cognizant of the potential early presentation of OPSCC, so a biopsy can be performed and treatment can be initiated while the tumors are in the earliest stage. Unfortunately, OPSCC is often diagnosed in the later stages when symptoms become more pronounced. If diagnosed in the early stages (ie, stage 1 or 2), the patient may only need surgery or radiation. Late-stage carcinomas may require a combination of surgery, radiation, and/or chemotherapy. In addition, patients with HPV-positive OPSCC have been shown to have a more favorable outcome and quality of life compared with HPV-negative patients, so this designation can be important when providing optimal cancer care to these patient populations.

RELATED: Head and Neck Cancer Resource Center

Recent studies show an associated risk for HPV-positive OPSCC as the number of sexual partners increases. For example, one case-control study found that the odds of oral HPV infection among young men of college age increases with the number of partners with whom they engaged in oral sex (P=0.046 for trend) or open-mouth kissed (P=0.02 for trend).3 D’Souza and colleagues also found that OPSCC is associated with a higher lifetime number of oral-sex partners (≥ 6; odds ratio [OR] 3.4; 95% CI, 1.1-8.8) and a higher number of vaginal-sex partners (≥26; OR 3.1; 95% CI, 1.5-6.5).4

Another important takeaway message from this study is that, not only do medical professionals now have the knowledge to identify symptoms of HPV-positive and HPV-negative OPSCC early, thus improving the chances for an improved outcome, but they also have the opportunity to relay the risk factors that can lead to HPV infection, thus empowering patients to make safer choices for the benefit of their own health.

Expert Opinion
Benjamin L. Judson, MD, MGA
Benjamin L. Judson, MD, MGA

It is already known that HPV-positive oropharyngeal cancers tend to have smaller primary tumors and bulkier cervical nodal disease. This study captures that difference from the perspective of how patients present.

The fact that patients’ first symptom with an HPV-positive oropharyngeal cancer is most frequently a neck mass highlights an important dilemma. Patients usually present with significant cervical metastasis, putting them at advanced stage, and leading to more intensive and potentially morbid treatment. On the other hand, we do not have screening tools or even guidelines for detecting this disease when the tumors are small and at an early stage.

Benjamin L. Judson, MD, MGA
Assistant Professor
Associate Residency Program Director
Section of Otololaryngology, Department of Surgery
Yale University School of Medicine
New Haven, CT


  1. Mehanna H, Beech T, Nicholson T, et al. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer-systematic review and meta-analysis of trends by time and region. Head Neck. 2013;35(5):747-755.
  2. McIlwain W, Sood A, Nguyen S, et al. Initial symptoms in patients with HPV-positive and HPV-negative oropharyngeal cancer. JAMA Otolaryngol Head Neck Surg. 2014 Mar 20 [Epub ahead of print].
  3. D’Souza G, Agrawal Y, Halpern J, et al. Oral sexual behaviors associated with prevalent oral human papillomavirus infection. J Infect Dis. 2009;199(9):1263-1269.
  4. D’Souza G, Kreimer AR, Viscidi R, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007;356(19):1944-1956.