Historically, many researchers and clinicians have grouped oral cavity and oropharyngeal cancers all together calling them "oral cancers".  It is now quite clear that oral cavity cancer (OCSCC) and oropharyngeal cancer (OPSCC) are two distinct cancers that differ in anatomic location, patient demographics, etiopathogenesis, presenting symptoms, treatment and survival.

Anatomy

Anatomically, the oral cavity consists of the lips, buccal mucosa, floor of mouth, alveolar ridge and gums, anterior 2/3 of the tongue, hard palate, and the retromolar trigone. Separate and distinctive, the oropharynx consists of the soft palate, base(or posterior 1/3) of tongue, tonsils, palatoglossus folds, valleculae, and the posterior pharyngeal wall. The anatomic border separating the two is, from above, the junction of the hard and soft palate, and from below, the circumvallate papilla. (FIGURE 1) 

FIGURE 1: Oral Cavity and Oropharynx anatomical locations.

Epidemiology

The incidence of oral cancer is decreasing while the incidence of oropharyngeal cancers is increasing. Patients with oral cancers (OCSCC) are more likely than oropharyngeal cancer (OPSCC) patients to use tobacco and alcohol, have less formal education, be African American, and to be in a lower socioeconomic level. (TABLE 1) Conversely, OPSCC cancer patients are more likely to have an HPV-associated cancer, are younger, more likely to be male, have a history of more oral sex/partners, be a non-smoker, European American, and at a higher socioeconomic status. (TABLE 2) Only about 15% of OCSCC are HPV positive while about 65% of OPSCC are HPV positive. Survival also appears to be lower in OCSCC than in OPSCC. 

FIGURE 2: Squamous cell carcinoma presenting as an area of erythroplakia on the ventrolateral tongue in the oral cavity.

FIGURE 3: Classic appearance of HPV associated OPSCC in a non-smoker.

TABLE 3: Initial presenting symptoms of patients with OPSCC

From: McIlwain, et al: JAMA Otolaryngol Head Neck Surg. 2014;140(5):441-447. doi:10.1001/jamaoto.2014.141 Published online March 20, 2014.

Imaging

FIGURE 4: Cystic neck mass with low FDG uptake with primary HPV associated OPSCC in base of tongue/tonsil.

Viral Testing

HPV testing is now the standard of care for all patients with OPSCC and/or an unknown primary. There are many types of HPV and the most common high-risk types related to cancer are HPV-16 and HPV-18. While work continues to identify a standardized, reliable and inexpensive detection assay, current testing may include p16 immunohistochemistry,  in situ hybridization, PCR, E6 Serum Antibodies; and combinations thereof. The p16 detection is highly sensitive and is the most common method used at the authors' institution while in-situ hybridization is more specific.

Treatment

The standard of care for treatment should follow the NCCN Guidelines when possible and appropriate for the individual patient.  Multidisciplinary care is important and should include surgery, radiation, medical oncology, dental oncology, and speech pathology among others.  Treatment remains stage directed and, as yet, no modifications are recommended based upon HPV status thus all cancers(HPV(+) and HPV(-)_are treated according to NCCN guidelines. 

The majority of both early and late OCSCC are treated surgically with clear 1-2 cm margins and neck dissection when clinically evident nodes or increased risk of occult metastasis. Advanced stage OCSCC(Stage 3/4) requires multimodality treatment with surgery as the initial treatment and finds surgical pathology dictating the need for adjuvant radiation or chemoradiation.  The treatment decision-making in OPSCC is slightly more complex.  For early stage cancers, either radiation alone or surgery alone is indicated while advanced staged cancers require combinations of either surgery followed by radiation or concomitant  chemotherapy and radiation therapy. (TABLE 2) Decision-making in this scenario is difficult as one cannot predict the functional and curative outcome prior to treatment.  When surgical resection is undertaken, several types of surgeries can be performed including the two common transoral methods: transoral robotic surgery (TORS) and transoral laser microsurgery (TLM) as well as the traditional approach (TOHS), transoral human surgery as coined by Dr. Joshua Hornig.

Summary

Cancers of the oral cavity and oropharynx represent more than just distinct anatomic sites.  The etiopathogenesis, diagnosis, treatment and outcomes have been diverging for over a decade.  It is important for the diagnosing and treating physicians to be aware of these differences and provide the multidisciplinary care and education necessary to optimize outcomes.  Treatment depends on the location and stage of the cancer.  Vaccination to prevent HPV infection may have the greatest potential to reduce the morbidity and mortality of oropharyngeal cancer that so far is rising in the United States.