25.1 Introduction

The hard palate is a bony structure formed by the palatine processes of the maxilla and the horizontal plates of the palatine bones and bounded anterolaterally by the alveolar ridge of the maxilla. The hard palate is covered by periosteum, submucosa containing neurovasculature and minor salivary glands laterally, mucosa, and keratinized stratified squamous epithelium. The upper border of the hard palate is the floor of the nasal cavity. ¹

The soft palate is a mobile fold of tissue attached to the posterior end of the hard palate and lateral walls of the oropharynx. The posterior muscular portion hangs between the oral cavity and oropharynx and is known as the velopharynx. The velopharynx closes off the nasopharynx during speech and swallowing by approximating with the posterior pharyngeal wall. The hard and soft palates are lined with stratified squamous epithelium on the inferior oral surface and ciliated columnar epithelium on the superior nasal surface. ¹

At least two-thirds of hard palate tumors, and up to 90% of hard palate malignancies, are squamous cell carcinoma (SCC). ^{2 , 3} Other tumors of the hard palate include minor salivary gland neoplasms such as adenoid cystic carcinoma, mucoepidermoid carcinomas, and adenocarcinomas. ⁴ About 80% of malignancies in the soft palate are SCC (SPSCC), while the remainder are typically of minor salivary gland origin. ^{5 – 7} SPSCC is more rare than SCC at other oropharyngeal sites, such as the tonsil or base of the tongue. ^{5 , 8} The management of palate SCC is important because of its significant impact on speech, mastication, and swallowing.

25.2 Epidemiology

The estimated incidence of oral cavity and oropharyngeal cancer for 2018 is 51,540 cases. ⁹ Hard palate cancers account for only about 5% of all oral cavity cancers. ⁴ SCC of the soft palate accounts for approximately 5-12% of oropharyngeal cancers. ¹⁰ According to data from the Surveillance, Epidemiology, and End Results (SEER) database, there were 4,366 cases of SPSCC recorded from 1973 to 2015 and 1,489 cases of hard palate SCC (HPSCC) from 1973 to 2014. ^{11 , 12} The mean age of presentation of HPSCC is approximately 60-70 years old, and there is a slight female predominance. ^{12 – 14} SPSCC typically affects patients in their 6th to 7th decade and the prevalence in men is more than double that in women. ^{15 – 18} Oral cavity and oropharyngeal SCC, including palate SCC, are associated with tobacco use and alcohol consumption. ¹⁹ The carcinogenic effects of alcohol and tobacco are dose-dependent and create a synergistic effect that dramatically increases the risk of developing upper aerodigestive tract SCC. ²⁰ HPSCC has been associated with reverse smoking practices in India and the Philippines as well as poor oral hygiene, mechanical irritation, poorly fitting dentures, and syphilis. ³

While human papilloma virus (HPV) related oropharyngeal squamous cell carcinoma (OPSCC) has been rising at epidemic rates, high risk HPV infection rates are significantly lower in soft palate and posterior pharyngeal wall tumors than in other regions of the oropharynx with tonsillar tissue. ^{21 , 22} Gelwan et al found that the HPV-positivity rate among soft palate tumors was as low as 3.1%, compared to a 92% rate of HPV in tonsillar tumors. ²¹ HPV’s predilection for lymphoepithelium, which has an incomplete basement membrane, explains why the infection rate of cancers in the lymphoid-rich tonsils is so much higher than in the soft palate. ^{21 , 22} HPV-mediated OPSCC do not demonstrate keratinization on histopathology and are often poorly differentated. ²³ In contrast, SPSCCs are histopathologically similar to smoking-related SCCs in the oral cavity that arise from squamous dysplasia of surface epithelium and feature keratinization. ²¹ Therefore, SPSCC often resembles more “traditional” head and neck cancer than the base of tongue or tonsillar subsites, and is more similar to oral cavity carcinoma in its epidemiology.

25.3 Clinical Presentation

HPSCC typically presents as an ulcerating lesion, which may be asymptomatic in early stages or painful in more advanced stages. ⁵ Presenting symptoms also include a palatal mass, bleeding, foul odor, ill-fitting dentures, or loose teeth. A classic presentation of an occult HPSCC is when there is a sudden ill-fitting tooth with pain that does not respond to dental management. Up to 70% of lesions may extend beyond the hard palate to the soft palate, gingiva, maxillary sinus, sphenopalatine foramen, pterygopalatine fossa, and skull base. ⁵

Early stage SPSCC often presents asymptomatically where the tumor is incidentally found by patients or physicians due to their visibility on routine examination. ^{5 , 7 , 17} Early lesions may present as leukoplakia (▶ Fig. 24.2) or erythroplakia. ²⁴ Patients may also present with painful ulceration and odynophagia. ^{5 , 17} More advanced cancers may cause velopharyngeal insufficiency (VPI), hypernasal speech, dysphagia, referred otalgia, trismus from involvement of the pterygoid muscles, hemoptysis, or neck mass in adults. ⁵

SPSCCs tend to grow submucosally and may extend laterally, anteriorly, or superiorly. ^{20 , 25} Nearly 50% of patients present with extension beyond the soft palate to sites which include, in order of frequency: the tonsil, retromolar trigone, inferior alveolar process, posterior tonsillar pillar, oropharyngeal wall, and base of the tongue. ⁸ Lesions that extend into the nasopharynx along the veli palatini muscles are associated with middle ear effusion. ^{25 , 26} Extension into the sphenopalatine foramen is associated with palatal swelling due to hypostasis. ²⁶ Malignant involvement of the trigeminal nerve in the sphenopalatine foramen or pterygopalatine fossa can cause numbness of the palate. ⁵

HPSCC infrequently involves neck metastases. ²⁷ However, lymph node metastases are present in about 60% of patients with SPSCC on presentation. ²⁵ About 25% of patients with SPSCC present with synchronous or metachronous cancers at other sites, most commonly on the floor of the mouth. ^{8 , 20}

25.4 Diagnosis and Evaluation

Evaluation of palate tumors begins with the history and physical. Physical examination should be done by inspection and palpation of the primary tumor to determine the extent of mucosal and submucosal spread. ²³ Loose dentition should be evaluated for possible malignant involvement of the tooth sockets and bone. ³ Nasal endoscopy is also critical to assess for involvement of the nasal surface of the palate. Neurologic evaluation of cranial nerves should be performed due to potential involvement in advanced cancers and to assess for functional impairment. ²³ An absent corneal reflex is indicative of extension to skull base through the foramen rotundum, foramen ovale, or inferior orbital fissure. Trismus, malocclusion, and pain are symptoms of invasion of the pterygoid muscles. The clinician should also assess for VPI by asking the patient about nasal regurgitation with oral intake and listening for hypernasality in the patient’s voice. Nodes should be palpated and size, number, irregular shape, attachment to other nodes, and mobility should be evaluated. ²³

The primary lesion, neck nodes, and distant metastatic sites should be biopsied. Transoral biopsy of the primary lesion can be completed in the office with local anesthesia. ⁵ An incision through the overlying mucosa may be required for large nonulcerated lesions. ⁵ Excisional biopsy may be performed for small lesions. ⁵ Biopsy results are essential to establish the tumor etiology and determine therapeutic management since salivary gland tumors are often treated with primary surgery. A greater tumor thickness on biopsy can be predictive of cervical node metastases. ²⁸

Panendoscopy (direct laryngoscopy, bronchoscopy, and esophagoscopy) under anesthesia is done to map the tumor, assess margins, and rule out synchronous second primary malignancies. ^{5 , 8 , 29} The utility of panendoscopy for detecting synchronous cancers is greater in patients with history of tobacco use than those with no history of tobacco use. ²⁹ Examination under anesthesia may be unnecessary in patients with very small tumors confined to the palate with all boundaries visible. In these cases, tumor mapping can be completed with flexible nasopharyngolaryngoscopy and transoral inspection and palpation. ²⁶

Maxillofacial and neck computed tomography (CT) with and without contrast and/or magnetic resonance imaging (MRI) provide information about primary tumor extent and nodal metastases. ^{3 , 23} Early soft palate tumors can be visualized as soft tissue swelling on imaging but can be difficult to assess radiologically until they are large. ²⁵ However, imaging has great utility in more extensive disease and in establishing nodal stage. Coronal CT images are used to visualize bony invasion of the hard palate and extension into the nasal fossa or maxillary sinus, while axial images can reveal extension along the pterygoid plates and muscles, infratemporal fossa, and masticator space. ^{25 , 26} Tumors invading the parapharyngeal and masticator spaces may feature carotid artery encasement or superior extension to the skull base. If the tumor encases more than 270 degrees of the carotid artery on axial imaging, resection of the vessel is likely needed during tumor excision, which often makes the tumor unresectable from a staging perspective. ²⁵ MRI can be used to assess perineural extension and dural invasion in cases of intracranial involvement. ²⁶ MRI is useful for evaluating hard palate tumors for perineural invasion, paranasal sinus involvement, dural extension, and associated inflammation. ⁵

CT is used to evaluate lymph node metastases, which are typically located in the upper and mid-jugular (levels II and III) or retropharyngeal lymph nodes (RPLNs). ^{23 , 25} Bilateral metastases are common. ²³ The overall rate of RPLN metastasis in oropharyngeal cancer ranges from 14.5 to 36%, with higher rates in the soft palate and retropharyngeal wall than in base of tongue and tonsil subsites. ³⁰ In contrast, RPLN metastasis from the hard palate and other oral cavity SCCs is uncommon. RPLNs are split into the lateral (Rouviere) and medial node chains; metastases almost always involve the lateral chains. ³¹ Retropharyngeal nodes may be easily overlooked because they appear isodense to the adjacent prevertebral muscles on CT unless they are cystic or necrotic. ²³ If the RPLN is negative on both positron emission tomography (PET)/CT and another imaging modality, dissection of the RPLN is not needed. PET/CT is accurate at predicting RPLN disease in patients with nodal disease persistent or recurrent after chemoradiation. Chest CT/MRI is also used to evaluate for lung metastases. PET/CT can be used to evaluate metastases to lung, bone, and liver in stages III-IV disease. ^{23 , 27} Liver function tests may be sufficient to rule out liver metastases. ²⁶

SPSCCs are staged using the oropharyngeal SCC staging guidelines from the 8th edition of the American Joint Committee on Cancer (AJCC). ²³ The AJCC recommends that all oropharyngeal cancers be tested for p16 overexpression on immunohistochemistry as a marker for HPV-mediated carcinogenesis. Tumors are classified as p16 overexpressing if they exhibit =+2/+3 nuclear staining intensity (with or without cytoplasmic staining) with =75% distribution. ²³ Oropharyngeal tumors that do not meet these criteria are considered p16 negative and staged by separate criteria. Oral cavity SCCs including HPSCC are staged separately using the AJCC 8th edition, and this staging now includes depth of invasion. Oral cavity SCCs are not routinely stained for p16. Based on evidence that SPSCC is more histologically similar to SCC of the oral cavity than the other oropharyngeal sites, Gelwan et al suggest that soft palate tumors need not be routinely stained for p16. This is because in nontonsillar tumors of the oropharynx, the likelihood of detecting HPV is < 3%, the detection of HPV has no current prognostic relevance, and the positive predictive value of p16 immunohistochemical staining as a marker for HPV infection is low. ²¹