Oropharyngeal Cancer

Steven H. Lin and Giuseppe Sanguineti

Background

What is the incidence of oropharyngeal cancer (OPC) in the U.S.?

~12,000 cases/yr of OPC in the U.S. (2008 data)

How does the incidence of OPC compare to that of other H&N sites?

The incidence of OPC is increasing, whereas cancer of other H&N sites is decreasing.

Is there a gender predilection for OPC?

Yes. Males are more commonly affected than females (3:1).

What are the 4 subsites of the oropharynx (OPX)?

Soft palate, tonsils, base of tongue (BOT), and pharyngeal wall

From which subsite do most OPCs arise?

The tonsil (ant tonsil pillar and fossa) is the most common primary site.

What are the borders of the OPX?

Anterior: oral tongue/circumvallate papillae
Superior: hard palate/soft palate junction
Inferior: valleculae
Posterior: pharyngeal wall
Lateral: tonsil

What 3 structures make up the walls of the tonsillar fossa?

Walls of the tonsillar fossa:

Ant tonsillar pillar (palatoglossus muscle)
Post tonsillar pillar (palatopharyngeal muscle)
Inf glossotonsillar sulcus

What are the 4 most important risk factors for the development of OPC?

Risk factors for developing OPC:

Smoking
Alcohol
HPV infection (HPV 16)
Betel nut consumption

What is the 1^st-echelon drainage region for most OPCs?

The 1^st-echelon drainage site for most OPCs is the level II (upper jugulodigastric) nodes.

Are skipped mets common for OPC?

No. Skipped mets are extremely rare in OPC (<1%).

What are the 2 most common histologies encountered in the OPX? Rare histologies?

Most common histologies: squamous cell carcinoma (SCC) (90%), non-Hodgkin lymphoma (10% tonsil, 2% BOT)
Rare histologies: lymphoepithelioma, adenoid cystic carcinoma, plasmacytoma, melanoma, small cell carcinoma, mets

What % of pts with OPC fail locoregionally vs. distantly?

50% of OPC pts fail locally, and 50% fail distantly.

How prevalent is HPV infection in OPC?

Depending on the series, ~40%–80% of OPCs are associated with HPV infection.

Which HPV serotype is most commonly associated with OPC?

HPV 16 is the most common serotype in OPC (80%–90%).

What is a surrogate marker of HPV infection in OPC that can be used as an indirect indication of HPV seropositivity?

The surrogate marker for HPV infection is p16 staining; E7 protein inactivates Rb, which upregulates p16.

Which pt population is most likely to present with HPV-related OPC?

Nonsmokers and nondrinkers are most likely to have HPV+ SCC of the OPX.

Do HPV+ or HPV+ OPC pts have a better prognosis?

HPV+ OPC pts have a better prognosis. Data from RTOG 0129 (Ang KK et al., NEJM 2010) showed better 3-yr OS (82.4% vs. 57.1%) and risk of death (HR 0.42) for HPV+ pts. Smoking was an independent poor prognostic factor.

What is the hypothesis behind why HPV+ OPC pts have a better prognosis?

HPV+ H&N cancers are usually in nonsmokers and nondrinkers, so p53 status is usually nonmutated; p53 mutation (which is common in non–HPV-related H&N cancers) predicts for a poor response to Tx.

Workup/Staging

What nerves are responsible for otalgia in cancers of the oral tongue, BOT, and larynx/hypopharynx (HPX)?

Oral tongue: CN V (auriculotemporal) → preauricular area
BOT: CN IX (Jacobson nerve) → tympanic cavity
Larynx/HPX: CN X (Arnold nerve) → postauricular area

What is the most common presentation of OPC?

The most common presentation is a neck mass, especially with HPV+ OPC.

What are additional common presenting Sx by OPX subsite?

Base of tongue: sore throat, dysphagia, otalgia, neck mass
Tonsils: sore throat, trismus, otalgia, neck mass
Soft palate: leukoplakia, sore throat with swallowing, trismus/perforation, phonation defect with advanced lesions
Pharyngeal wall: pain/odynophagia, bleeding

Describe the workup for a pt with an OPX mass.

OPX mass workup: H&P (bimanual exam of the floor of mouth), labs, direct laryngoscopy, CT/MRI H&N, tissue Bx (EUA if necessary), and CXR (or CT chest)

If the neck mass Bx is positive, is an additional Bx of the primary lesion necessary?

Yes. A Bx of the primary (or suspected primary) should also be done.

What % of OPC pts have clinically occult nodal mets?

30%–50% of OPC pts have clinically occult nodal mets.

What % of OPC pts present with clinically+ nodes, and what % present with bilat nodal Dz?

~75% of OPC pts have clinically+ nodes at presentation, with ~30% having bilat Dz (especially if lesions are BOT/midline).

What is the T staging of OPC?

T staging of OPC is similar to other SOOTH (salivary, oral cavity, oropharynx, thyroid, hypopharynx) H&N cancers:

T1: ≤2 cm
T2: 2–4 cm
T3: >4 cm
T4a (moderately advanced): invades larynx, deep/extrinsic tongue muscles, medial pterygoid, hard palate, mandible
T4b (very advanced): invades lat pterygoid muscle, pterygoid plate, lat nasopharynx, skull invasion, carotid encasement