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gery, radiation therapy, cytotoxic chemotherapy, targeted systemic therapy, and immunotherapy. Management of complex oral cavity cancers benets from multidisciplinary team approach inclusive of allied health professionals.

References

1. Montero PH, Patel SG.Cancer of the oral cavity. Surg Oncol Clin N Am. 2015;24(3):491–508. https://doi.

org/10.1016/j.soc.2015.03.006. Epub 2015 Apr 15.

PMID: 25979396; PMCID: PMC5018209

2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F.Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. https://doi.

org/10.3322/caac.21660. Epub 2021 Feb 4

3. Ng JH, Iyer NG, Tan MH, Edgren G.Changing epidemiology of oral squamous cell carcinoma of the tongue: a global study. Head Neck. 2017;39(2):297–

304. https://doi.org/10.1002/hed.24589. Epub 2016 Oct 3

4. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67(2):93–9. https://doi.org/10.3322/caac.21388. Epub 2017 Jan 17

5. Pster DG, Spencer S, Adelstein D, Adkins D, Anzai Y, Brizel DM, Bruce JY, Busse PM, Caudell JJ, Cmelak AJ, Colevas AD, Eisele DW, Fenton M, Foote RL, Galloway T, Gillison ML, Haddad RI, Hicks WL, Hitchcock YJ, Jimeno A, Leizman D, Maghami E, Mell LK, Mittal BB, Pinto HA, Ridge JA, Rocco JW, Rodriguez CP, Shah JP, Weber RS, Weinstein G, Witek M, Worden F, Yom SS, Zhen W, Burns JL, Darlow SD.Head and neck cancers, version 2.2020, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2020;18(7):873–98. https://doi.

org/10.6004/jnccn.2020.0031.

6. Iyer NG, Tan DS, Tan VK, Wang W, Hwang J, Tan NC, Sivanandan R, Tan HK, Lim WT, Ang MK, Wee J, Soo KC, Tan EH. Randomized trial comparing surgery and adjuvant radiotherapy versus concurrent chemoradiotherapy in patients with advanced, nonmetastatic squamous cell carcinoma of the head and neck: 10-year update and subset analysis. Cancer. 2015;121(10):1599–607. https://doi.org/10.1002/

cncr.29251. Epub 2015 Jan 29. Erratum in: Cancer.

2015;121(19):3560

7. Tam S, Amit M, Zafereo M, Bell D, Weber RS.Depth of invasion as a predictor of nodal disease and survival in patients with oral tongue squamous cell carcinoma. Head Neck. 2019;41(1):177–84. https://doi.

org/10.1002/hed.25506. Epub 2018 Dec 7

8. Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK, Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for highrisk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004;350(19):1937–44. https://doi.

org/10.1056/NEJMoa032646.

9. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssouan H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567–78. https://doi.

org/10.1056/NEJMoa053422.

10. Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G Jr, Psyrri A, Basté N, Neupane P, Bratland Å, Fuereder T, Hughes BGM, Mesía R, Ngamphaiboon N, Rordorf T, Wan Ishak WZ, Hong RL, González Mendoza R, Roy A, Zhang Y, Gumuscu B, Cheng JD, Jin F, Rischin D, KEYNOTE-048 Investigators. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):1915–28. https://doi.org/10.1016/

S0140- 6736(19)32591- 7. Epub 2019 Nov 1. Erratum

in: Lancet. 2020;395(10220):272. Erratum in: Lancet. 2020 Feb 22;395(10224):564. Erratum in: Lancet. 2021;397(10291):2252

Mucosal Malignancy: Cancers

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oftheOropharynx

JoelC.Davies, SusannahC.Orzell, andDannyJ.Enepekides

13.1 Background: Scope oftheProblem

Our understanding of the complexities of cancer of the oropharynx has changed dramatically over time. Prior to the 1980s, the majority of patients presenting with oropharynx cancer had risk factors which were common to other sites of the head and neck, primarily exposure to tobacco and alcohol consumption [1, 2]. However, over the last two to three decades, there has been a rapid shift away from tumors that are driven by traditional risk factors such as alcohol and tobacco [2]. These patients presenting tended to be younger (40–59) and male [1]. It was discovered that in these patients, cancer of the oropharynx was driven by a viral-mediated mechanism through exposure to high-risk subtypes of the Human Papillomavirus (HPV) [3]. The rise of HPV-positive oropharyngeal cancer over the past few decades is signicant and, since 2009, has

J. C. Davies Department of Otolaryngology-Head and Neck Surgery, Sinai Health System, University of Toronto, Toronto, ON, Canada e-mail: Joel.Davies@sinaihealth.ca

S. C. Orzell · D. J. Enepekides (*) Department of Otolaryngology-Head and Neck Surgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada e-mail: susannah.orzell@uhn.ca;

danny.enepekides@sunnybrook.ca

surpassed that of cervical cancer [4]. Approximately 14,000 new cases of oropharynx were diagnosed in the USA in 2013 and account for 10–12% of all upper aerodigestive tract malignancies [2]. Although based on histology, the majority (>90%) of cancers in the oropharynx are squamous cell carcinomas (SCCs), at a cellular level 70% are now HPV-positive SCCs with the remainder being HPV-negative or indeterminate [1]. The most common subtypes of HPV associated with oropharyngeal cancer include HPV 16,18, 31, 33, and 35, with type 16 comprising close to 90% of HPV-positive OPSCC [5]. While tobacco and alcohol consumptions are the major risk factors for development of HPVnegative OPSCC, number of sexual partners and oral infection with HPV are the risk factors most associated with HPV-positive OPSCC [3, 6]. Given these known risk factors, physicians should be aware of the importance of recommending HPV vaccination in younger cohorts of boys and girls. Currently, the CDC recommends vaccination for boys and girls up to age 26 with a target of these patients receiving vaccination prior to their rst sexual contact [5].

The prognosis of oropharynx cancer is highly dependent on HPV status and, to a lesser degree, the location of the primary tumor. Generally, those patients with HPV-positive malignancies tend to have a more favourable prognosis and this has been reected in the most recent editions of the AJCC staging guidelines. For example, a

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189

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3cm HPV-positive tumor of the tonsil with three ipsilateral-positive lymph nodes measuring 2cm each without distant metastatic disease would be staged as cT2N1M0 (overall stage I) with a 5-year overall survival of 85% [7]. However, a tumor with the same dimensions and clinical prole that is HPV-negative would be staged as cT2N2bM0 (overall stage 4a) with a 5-year overall survival of 45% [7]. As a clinician evaluating a patient presenting with a tumor of the oropharynx, understanding the etiologic, clinical, and treatment-related differences between the two distinct entities is of utmost importance and will be the primary focus of this chapter.

13.2 Anatomy oftheOropharynx

The oropharynx is sub-divided into anatomic subsites including the tonsil, soft palate, base of tongue, and posterior pharyngeal wall (Fig.13.1). It is bordered superiorly by the soft palate and inferiorly by the valleculae and hyoid bone. The circumvallate papillae form the anterior extent and the posterior pharyngeal wall the posterior extent. The lateral oropharynx is bounded by the palatine tonsils.

The soft palate originates at the posterior extent of the hard palate and is mainly comprised of skeletal muscle capable of tensing and elevating the palate. The primary function of the soft palate is to close off and separate the oropharynx from the oral cavity and nasopharynx. The palatine tonsils are comprised of lymphoid tissue and are located between the anterior and posterior tonsillar pillars which are formed by the palatoglossus and palatopharyngeal muscles, respectively. The base of tongue extends posteriorly from the circumvallate papillae back to the valleculae. The supercial base of tongue is predominantly lymphoid tissue, while the deep tongue is skeletal muscle. The posterior pharyngeal wall is formed by the superior constrictors and the mucosa overlying these constrictors. It extends superiorly from the soft palate and inferi-

J. C. Davies et al.

Fig. 13.1 Diagram of the upper aerodigestive tract (dark blue) demonstrating the oropharynx (red), including subsites: (a) soft palate, (b) palatine tonsils, (c) base of tongue, and (d) posterior pharyngeal wall

orly down to the attachment of the epiglottis to the thyroid cartilage.

13.3 Key Elements ofHistory

13.3.1 Signs andSymptoms ofOropharynx Cancer

While patients with oropharyngeal cancer may be referred with an obvious tumor of the tonsil or soft palate, these tumors may begin very small within tonsillar crypts or deep in the base of

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tongue. As a result, these tumors may go unnoticed for months or years before presenting for evaluation. Therefore, clinicians must be judicious in evaluation patients presenting with subtle signs and symptoms of oropharyngeal cancer.

Common presenting symptoms of oropharynx

cancer:

• Dysphagia.

• Odynophagia.

• Otalgia.

• Pain.

• Globus sensation.

Common presenting signs of oropharynx

cancer:

• Neck mass.

• Oral bleeding.

• Palpable mass in subsite of oropharynx.

Tumors of the oropharynx most commonly present within the tonsil. These patients will frequently complain of dysphagia, otalgia mufed voice, and/or trismus. The second most common subsite affected by oropharyngeal cancer is the base of tongue. Given that these tumors may be deep and, therefore difcult to detect, they more often present at an advanced stage. Common symptoms include dysphagia, ipsilateral referred otalgia, oral bleeding, and/or globus sensation. Oropharyngeal tumors of the soft palate are the third most common. These tumors, like tonsillar tumors, are more easily detected and therefore present at an earlier stage. Signs and symptoms are similar to tonsillar cancers. Lastly, tumors of the posterior pharyngeal wall are among the rarest of oropharynx cancers. Symptoms at presentation include dysphagia, odynophagia, and bleeding. Of note, all tumors of the oropharynx, with the exception of the tonsil, have bilateral lymphatic drainage to the neck and most commonly within levels II-IV. Therefore, a patient presenting with a neck mass within any combination of unilateral, contralateral, or bilateral levels II-IV must be examined for an oropharyngeal primary cancer.

13.3.2 Social andSexual History

Although pathologic diagnosis is required to conrm HPV status, clinical suspicion may be heightened by obtaining a careful history. Specically, social history can reveal important clues such as common risk factors for HPVnegative- driven cancers including exposure to tobacco and alcohol. A discussion regarding sexual history including number of sexual partners and age of rst encounter with oral/vaginal intercourse is important as these factors have been found to be associated with HPV-positive OPSCC. For example, D’Souza et al. (2007) observed that high lifetime number of vaginalsex (≥26) and oral-sex (≥6) partners was associated with HPV-positive OPSCC [6]. Lastly, there is some literature to suggest that marijuana users may be at an elevated risk for developing HPVpositive oropharyngeal cancer [8]. However, it is difcult to assess whether it is marijuana use itself or characteristics of the population using marijuana that increase their risk.

13.3.3 Special Consideration ofCancer ofUnknown Primary

Although many patients may present with symptoms and signs of oropharynx cancer and have their primary tumors found during physical examination, a certain subset of these patients will present with a cervical lymph node that is positive for malignancy without an obvious primary tumor. Although a discussion regarding the workup of cancer of unknown primary (CUP) of the neck may be covered elsewhere in this book, it is important that clinicians be aware of the high likelihood that these CUPs are oropharyngeal tumors that are often too small to detect clinically. Close to 90% of all CUPs of the neck are metastases from oropharyngeal tumors and are approximately equally divided between the tonsil and base of tongue [5]. These patients tend to present with lymph nodes in levels II-IV that are cystic in nature and, despite small occult prima-

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ries, the nodes can be large. Although there are many benign etiologies with a similar presentation, one must always consider an oropharyngeal primary tumor in evaluating a patient presenting with a cystic lymph node of the neck.

13.4 Clinical Examination Pearls

As with other sites, evaluation of the oropharynx begins with a thorough inspection of the various subsites including the palatine tonsils, soft palate, base of tongue, and posterior pharyngeal wall. However, unlike the oral cavity, small tumors may be hidden from plain sight deep within crypts of the base of tongue or tonsil. Therefore, it is critical that the next stage of evaluation includes palpation of these areas. The examination continues with endoscopy (exible or rigid) to further evaluate the base of tongue, posterior pharyngeal wall, and posterior palatine tonsils. It is important to provide the patient with topical anaesthetic/decongestant prior to evaluation to improve comfort and facilitate an accurate examination. During the examination, having a patient protrude their tongue can assist in identifying small base of tongue tumors. As an adjunct to an endoscopic examination, narrow band imaging may be performed to detect pre-malignant and early malignant tumors which otherwise may not be clinically apparent. Narrow band imaging has been demonstrated to provide a more accurate diagnostic assessment of malignancy than white light imaging [5]. If a tumor is identied during the examination, biopsies can be obtained through using a transnasal approach via side channels of a transnasal endoscope or transorally while simultaneously performing endoscopy. Lastly, bimanual palpation of the neck is required to identify and characterize lymph nodes of the neck to assess for possible regional metastases.

Although included within the next section on investigations, panendoscopy should also be considered an important part of the clinical examination as a more thorough assessment of the subsites can be performed with the patient under general anaesthesia.

13.5 Investigations andLimitations

13.5.1 Biopsy ofthePrimary Site

Prior to the commencement of treatment planning, a biopsy with histopathologic evaluation and immunohistochemistry is required. Many primary tumors of the oropharynx are amenable to transoral biopsy and are frequently performed safely in the ofce setting under local anesthetic. If there is concern about the vascularity of the tumor, such as when a neurobroma or hemangioma is suspected, a transoral biopsy in the ofce setting may not be appropriate. Visible tumors of the oropharynx not accessible transorally may still be amenable to an in-ofce biopsy with a transnasal endoscope.

13.5.2 Biopsy ofaLymph Node

The initial presenting symptom for many oropharyngeal squamous cell carcinomas is a neck mass related to a metastatic disease within a lymph node, most often in the upper jugulodigastric lymphatic basin. HPV-associated tumors in particular are associated with early metastases to cervical lymph nodes, even with small or nonexistent primary tumors in the oropharynx. When a patient presents with an abnormal cervical lymph node, a ne needle aspiration biopsy (FNAB) may be performed in order to obtain a diagnosis. This procedure may be performed in the ofce or by an interventional radiologist, and ultrasound guidance is frequently employed. It is not uncommon for metastatic lymph nodes to have central necrosis, thus complicating needle biopsy procedures as the necrotic material is generally unhelpful for diagnosis. If a FNAB is nondiagnostic, it may be either repeated or a core needle biopsy can be pursued. Where FNAB typically uses a small gauge needle, a core needle biopsy often uses an 18 gauge or higher bore and thus is able to obtain more cellular material. A core needle is also advantageous if lymphoma is suspected, as it has a higher diagnostic yield

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compared to FNAB [9]. Excisional biopsies are considered the gold standard for diagnosing lymphoma, but are generally not recommended when metastatic disease is suspected.

13.5.3 Histopathology andImmunohistochemistry

Squamous cell carcinomas of the upper aerodigestive tract are often differentiated into keratinizing or non-keratinizing subtypes, where the latter is associated with HPV-related disease. Comprehensive evaluation of an oropharyngeal squamous cell carcinoma must include testing for HPV or surrogate markers. The tumor suppressor p16 is most commonly used as a surrogate marker to diagnose HPV-related disease, although several other modalities may be used, such as in situ hybridization (ISH) and polymerase chain reaction (PCR). A threshold of 70% or more nuclear and cytoplasmic expression of p16 on immunohistochemistry is recommended by the American Society of Clinical Oncology (ASCO) to diagnose HPV-related squamous cell carcinoma in the oropharynx. Despite the high sensitivity, ease, and cost-effectiveness of p16 testing, it is not considered the gold standard since it is an indirect marker of HPV infection and other pathologic processes may lead to an increase in p16. Thus, in cases where the p16 results are discordant with other information and ndings (e.g. a young, non-smoker with p16-negative nonkeratinizing oropharyngeal squamous cell carcinoma), further testing with ISH or PCR may be warranted.

13.5.4 Panendoscopy

A panendoscopy refers to the comprehensive physical examination of the upper aerodigestive tract under general anesthesia. This is accomplished by both bimanual examination of the oral cavity and accessible parts of the oropharynx/supraglottis, as well as exible or rigid endoscopic instruments that can be used to visualize the nasal cavity, nasopharynx, oropharynx, larynx, esophagus, trachea, and mainstem bron-

chi. A panendoscopy may be performed when a patient has a tumor that is inaccessible for biopsy in the ofce setting, or if a patient presents with a neck metastasis and there is no obvious primary tumor on examination. Further evaluation under general anesthesia often affords the surgeon the ability to very closely inspect areas that are difcult to examine in the awake patient, determine the extent of the tumor, evaluate for second primary malignancies, and to perform more extensive biopsies. In some patients, deep biopsies of the tongue base and tonsils are required for diagnosis, which can be very challenging outside of the operating room. Performing biopsies in the operating room also gives the surgeon the opportunity to send specimens for frozen section analysis. If a primary tumor is unable to be identied on physical exam or panendoscopy (CUP), the surgeon may elect to do a concurrent tonsillectomy, base of tongue resection, or a combination of the two in an effort to identify the site [10, 11].

13.5.5 Imaging

As with histologic conrmation of disease, imaging of the primary site as well as sites of possible regional and distant metastasis is essential for staging and treatment planning in patients with oropharyngeal cancer. CT and MRI are commonly employed to characterize lesions and metastatic sites in the head and neck. The choice of study depends on the clinical suspicion and questions about what structures may or may not be involved with the tumor. CT has the advantage over MRI for evaluation of bony invasion and is faster and often easier to obtain, whereas MRI has superior soft tissue denition and can demonstrate perineural spread of disease. CT thorax or PET/CT are appropriate to evaluate for distant metastasis, with PET/CT having slightly higher detection rates of distant metastasis compared to CT thorax [12]. In the case of a patient with an unknown primary tumor, PET/CT has demonstrated utility in indicating the source [13].

• Staging (Tables 13.1 and 13.2—OPSCC HPV- vs HPV+)

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Table 13.1 AJCC ninth edition TNM staging for the oropharynx (p16/HPV-)

T category Tx Primary tumor cannot be assessed

Tis Carcinoma in situ T1 Tumor 2cm or smaller in greatest dimension T2 Tumor larger than 2cm, but not larger than 4cm in greatest dimension T3 Tumor larger than 4cm in greatest dimension or extension to lingual surface of

epiglottis

T4a Moderately advanced local disease. Tumor invades the larynx, extrinsic muscle of the

tongue, medial pterygoid, hard palate, or mandible

T4b Very advanced local disease. Tumor invades lateral pterygoid muscle, pterygoid plates,

N category Nx Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis N1

N2a

N2b

N2c

N3a

N3b Metastasis in any node and clinically overt ENE (+)

Denotes pathologic staging

lateral nasopharynx, or skull base or encases carotid artery

Metastasis in a single ipsilateral lymph node, ≤3cm and ENE(−)

Metastasis in a single ipsilateral lymph node, 3–6cm and ENE(−)

Metastasis in single ipsilateral node ≤3cm and ENE(−)

Metastasis in a multiple ipsilateral lymph node, ≤6cm and ENE(−)

Metastasis in bilateral or contralateral lymph nodes, ≤6cm and ENE(−)

Metastasis in a lymph node >6cm and ENE(−)

Metastasis in single ipsilateral node≥3cm and ENE (+); or multiple, ipsilateral, contralateral, or bilateral nodes, any with ENE (+) or a single contralateral node of any size and ENE (+)

J. C. Davies et al.

Table 13.2 AJCC ninth edition TNM staging for the oropharynx (p16/HPV+)

T Category T0 No primary tumor identied

T2 Tumor 2-4cm T3 Tumor >4cm or extension to lingual surface of epiglottis T4 Tumor invades larynx, extrinsic tongue muscle, medial

N category Nx Regional lymph nodes cannot be assessed

N0 No regional lymph nodes metastasis N1

N3 Lymph node >6cm

Denotes pathologic staging

13.6 Management ofOPSCC

Tumor ≤2cm

pterygoid, hard palate or mandible, or beyond

One or more ipsilateral lymph nodes (≤6cm)

Metastasis in ≤4 lymph nodes

Contralateral or bilateral lymph nodes (≤6cm)

Metastasis in >4 lymph nodes

patients to receive adjuvant radiation, these adverse effects were then further compounded.

The past several decades have seen numerous signicant changes in the treatment for OPSCC. Historically, oropharyngeal tumors were treated surgically via transcervical and transfacial incisions with a mandibulotomy for access. These approaches had a high potential for both disgurement and oropharyngeal dysfunction, and since it was common for many of these

Regarding non-surgical treatment, radiation with or without chemotherapy offers very favorable locoregional control rates, but also has several short- and long-term associated toxicities. Dysphagia and oropharyngeal dysfunction are common with both surgical and non-surgical management of OPSCC, but CRT can also induce signicant brosis, trismus, mucositis, and xero-

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stomia (which itself can predispose patients to dental caries, periodontal disease, and recurrent infections) depending on treatment site [14]. A dreaded complication of radiation therapy is osteoradionecrosis, which most often occurs in radiated areas of the mandible and can lead to pathologic fractures and chronic infections, both of which are extremely problematic and difcult to treat. The psychosocial impact is enormous no matter what the treatment modality, and depression is highly prevalent within the head and neck cancer patient population [15, 16].

In recognition of the numerous physical and psychosocial side effects of both surgical and non-surgical treatment, the modern paradigm for treatment of OPSCC has paid particular attention to maximizing function and quality of life. The formation of multidisciplinary teams composed of surgeons, radiation oncologists, medical oncologists, speech-language pathologist, and other specialists has allowed for greater discourse and personalized treatment in an effort to identify treatments that achieve both disease remission and retain function and maintain quality of life. This has been particularly important due to several recent changes in both the etiology of disease and treatment options available. HPV-positive OPSCC is not only a demographically different disease from HPV-negative OPSCC, but a biologically distinct disease as well. HPV-positive OPSCC is much more sensitive to chemotherapy and radiation (CRT) regimens compared to HPVnegative OPSCC [17], and thus the former has a much higher survival rate with CRT [18].

Additionally, there have been several technological advances within the surgical and non-surgical realms. The introduction of intensity modulated radiation therapy (IMRT), which allows for more precision in the delivery of radiation, and transoral surgery (TOS), which includes trans oral robotic surgery (TORS) and transoral laser microsurgery (TLM), have both presented new treatment options. These innovations have allowed for more exploration into deintensifying treatment regimens, which is particularly important in HPV-positive OPSCC as these patients are younger, and therefore will have to live longer with the effects of their treatment. Furthermore, there is the concern about a radiation-induced second primary malignancy, which would likely affect a younger cohort considering it may take decades to become apparent.

The introduction of TOS as an option for treatment of selected early stage OPSCC has allowed for some patients to avoid radiation altogether, or be treated with lower dose radiation and still maintain high rates of cure with lower rates of adverse effects and a higher quality of life [19]. TOS is not an option for every patient with OPSCC. The ideal TOS patient has a small (cT1/2) exophytic, lateralized tumor, and limited or no clinical evidence of metastatic disease in the neck. Contraindications to TOS can be divided into vascular, functional, oncologic, and general factors [20] (Fig.13.2).

Regarding non-surgical treatment, some studies have found that reducing radiation therapy to as little as half of a traditional dosing regimen

Fig. 13.2 (a) Setup for transoral robotic surgery. (b) Intraoperative image of transoral robotic resection of left base of tongue tumor

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has comparable cure rates with signicantly better quality of life metrics [21]. In a comparison of TOS and CRT, TOS did have higher rates of dysphagia, though this was not signicant [22]. At this time, CRT is favored as the preferred method of treatment for OPSCC though there are still many questions yet to be answered about which treatment regimen is truly superior. One principal that most will agree on is that triple modality therapy (i.e. surgery with adjuvant CRT) is to be avoided, if possible. Each option has its advantages and disadvantages, and so the decision making process must be patient-centered. At this time, there are several ongoing studies examining cure rates and quality of life metrics for various treatment regimens. This ever-changing landscape and nuance in different regimens highlights the importance of the multidisciplinary care team as well as the vigilance of the participants in keeping up to date with the newest ndings.

13.6.1 Management by Clinical Stage

• Denitive RT.

• P16/HPV- T1-2N0–1. – P16/HPV + T1-2N0 and T0-2N1 (single

node ≤3cm).

– Denitive radiation treatment to the pri-

mary site, ipsilateral neck, and possibly the contralateral neck (consider for tumors of the tongue base, posterior pharynx, and soft palate).

• Resection of primary and neck dissection. – P16/HPV- T1-2N0–1 and T1-4aN0–3. – P16/HPV + T1-2N0–1, T0–3N3 or

T4N0–3.

– TOS: Eligible candidates may undergo

TLM or TORS for resection of the primary tumor.

– TOS is rarely a safe option for patients with

T3-T4a disease. The majority of cases treated surgically are accessed via open approaches (transfacial and transcervical incisions).

– Neck dissection: At least an ipsilateral neck

dissection is performed. A contralateral

neck dissection is considered for tumors of the tongue base, posterior pharynx, and soft palate.

– Adjuvant RT/CRT may be required for

adverse features on pathological analysis.

• Concurrent CRT.

• P16/HPV- T1-2N0–1 and T1-4aN0–3.

• P16/HPV+T0-2N0–1, T0–3N3 or T4N0–3.

• Cisplatin (cetuximab for patients unable to tolerate cisplatin) should be considered for N1 disease, in addition to denitive RT.

• Induction chemotherapy followed by RT or CRT.

• P16/HPV- T1-4aN0–3.

• P16/HPV+ T0-2N1 (single node >3cm or 2 or more ipsilateral nodes ≤6 cm), T0–3N3 or T4N0–3.

• Unlike the previous options, there is signicant disagreement about the propriety of this option. This option is typically considered for very complex cases.

• This option may be considered in the context of a clinical trial.

Top Five Takeaways

1. Distinct anatomic subsites with variations in

etiology of OPSCC.

2. Evolving demographic secondary to HPV

infections.

3. Role of panenodoscopy in diagnosis of both

evident and occult primary lesions.

4. Despite de-intensication trials to reduce

impact on QOL metrics, standard of care remains centred on concurrent CRT.

5. Importance of early detection and treatment.

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