**4. Treatment and outcome**

*Human Papillomavirus*

I T0-T2

II T0-T2

III T0-T3

**Tumor Characteristics**

T0 No primary tumor identified

*AJCC staging of HPV-positive (p16+) oropharyngeal cancer [14].*

T0-T2

T3

T4

T2 Tumor between 2 and 4 cm

epiglottis

N1 One or more ipsilateral lymph nodes, none

N2 Contralateral or bilateral lymph nodes, none

>6 cm

>6 cm

N3 Lymph node(s) > 6 cm

T1 Tumor less than 2 cm in any dimension

**24**

foreign materials.

**Table 2.**

**Table 3.**

**Lymph node (N)**

**Table 1.**

ment (N), and the existence of metastases (M).

currently used for detecting HPV presence [15].

staging and should include the skull base, cervical region, thorax, and abdomen to possibly identify secondary tumors. Contrast-enhanced MRI is superior to CT in detecting soft tissue extension and involvement but may be influenced by dental

*AJCC lymph node characteristics for staging of disease regarding HPV-positive (p16+) oropharyngeal cancer.*

T3 Tumor greater than 4 cm in any dimension or extension to lingual surface of the

**Stage T N M**

IV T Any N Any M1

N0 N1

N2 N0-N2

N3 N0-N3 M0 M0

M0 M0

M0

*AJCC tumor characteristics regarding HPV-positive (p16+) oropharyngeal carcinoma [14].*

T4 = moderately advanced local disease—tumor invades the larynx, extrinsic muscles of the tongue, medial pterygoid muscles, hard palate, mandible or beyond

**Clinical N (cN) Pathological N (pN)**

assessed

nodes

Metastasis in 4 or fewer lymph nodes

Metastasis in more than 4 lymph

Nx Regional lymph nodes cannot be assessed Regional lymph nodes cannot be

N0 No regional lymph node metastasis No regional lymph node metastasis

Starting from 1 January 2017, all patients with oropharyngeal cancer should be tested for the presence of HPV, thus classifying them in one of two possible categories—HPV positive (p16INK4A+) and HPV negative. There is no current gold standard test, because all available testing methods were developed for cervical cancer, and not perfectly adapted for tonsillar cancer. However, p16 protein IHC is

Staging of the disease is done by using the AJCC cancer staging system (**Table 1**) that uses three variables—primary tumor characteristics (T), lymph node involve-

Treatment of oropharyngeal malignancy depends on the disease stage, but the principle that guides it is the same as in all cancer surgery: local disease control. Thus, with modern surgical and irradiation techniques, 5-year survival rates of almost 100% are attainable [16].

For the purpose of management protocol, oropharyngeal cancer is divided into early-stage (T1 and T2) and advanced diseases (T3 and T4). The latter are divided into resectable and non-resectable tumors. According to this, treatment for early-stage disease should be either surgery or radiation therapy with concurrent chemotherapy. Surgical treatment consists of excision of the primary tumor, either by a trans-oral approach or by external approach (lateral pharyngotomy or transmandibular approach by mandibular swing technique (**Figures 3**–**5**)).

Most oropharyngeal tumors are accessible by trans-oral approach. This is the least aggressive type of surgical approach, with the least morbidity. Auto-static mouth gags (McIver, Dingmann, etc.) permit good exposure of the surgical site, and excision by electrocautery, radiofrequency, and CO2 laser, and optical augmentation either using surgical loupes or operating microscopes permit tackling most of the T1 to T3 tumors [17].

Tumors extending downward to the epiglottis and hypopharynx (pyriform sinus) require an external approach, by lateral pharyngotomy. This approach provides access to the oro- and hypopharynx, as well as control of the cervical large blood vessels and lymph nodes [18–20].

Advanced tumors (T4), tumors which involve adjacent structures (extrinsic muscles of the tongue, larynx, mandible, pterygoid muscles, or hard palate), often require an even more aggressive external approach—by lateral mandibulotomy the so-called mandibular swing technique. This approach permits access to the

### **Figure 3.**

*External approach to a right side advanced (T4) oropharyngeal cancer which shows the neck dissection, with internal jugular vein and bifurcation of the common carotid artery visible inferior to the posterior belly of the omohyoid muscle, as well as the mandibulotomy—The creation of the mandibular "swing."*

### **Figure 4.**

*External approach to a left side advanced oropharyngeal tumor, via mandibular "swing" demonstrating closure of the mandibulotomy using two titanium miniplates anchored with screws.*

### **Figure 5.**

*Extensive external approach to a left side advanced (T4) tumor of the oropharynx and hypopharynx extending to the bony cortex of the mandible—with modified radical neck dissection and lateral mandibulotomy, with the two resulting mandibular pieces being pulled apart at different angles so as to permit wider access.*

oral cavity, oropharynx, as well as hypopharynx and lateral cervical lymph nodes, parapharyngeal space, and masticator space and allows instrumentation of the entire oral cavity, making hard palate resections possible [21, 22].

Whichever surgical approach to the primary tumor the surgeon opts for, just as important as the complete excision of the tumor (the T) is the neck dissection. Tumors that do not pass the midline usually require ipsilateral lymph node dissection. However, bilateral neck dissection is sometimes required because of the vast network of lymphatics that drain the lateral pharyngeal area—most patients present with at least clinically N1 on diagnosis [23, 24].

The alternative to surgical excision of the tumor is external intensity-modulated radiation therapy (IMRT) with or without adjuvant chemotherapy. This procedure has similar outcomes compared to surgery in cases of early-stage tumors but is slightly inferior compared to surgery when addressing advanced tumors. The dose delivered to the surrounding tissues is responsible for the toxicity and late adverse

**27**

*HPV-Positive Oral Squamous Cell Carcinoma DOI: http://dx.doi.org/10.5772/intechopen.90954*

radiation therapy [25].

following surgical excision.

**5. Conclusions**

**Author details**

Bucharest, Romania

and Mihnea Cojocărița-Condeescu1

provided the original work is properly cited.

effects of radiation therapy, such as osteoradionecrosis of the mandible, radiomucositis, xerostomia, dental cavities, and teeth avulsion [25]. These have a high impact on the patients' quality of life; thus modern management of HPV-positive oropharyngeal cancer consists in trans-oral excision (with a rising trend towards robotic surgery) of the primary tumor with selective neck dissection followed by low-dose

As HPV infection is a growing concern worldwide, cases of HPV-positive oral and oropharyngeal carcinoma become more frequently encountered. Treatment options for this type of malignancy follow the same principles as for non-HPVpositive squamous cell carcinoma of the oral cavity and pharynx, consisting in surgery for locoregional control of the primary tumor and regional lymph nodes and radiation therapy—either as a stand-alone option or as an adjuvant therapy

However, particularities of HPV-positive oropharyngeal cancer have led to a separation of this pathologic entity from the rest of squamous cell carcinomas involving the oropharynx. These tumors have a better outcome following treatment and thus treatment options were de-escalated to offer the same outcome and 5-year

New perspectives in treating the chronic HPV infection as well as preventing this infection by introducing efficient vaccination programs that target girls and boys also offer a positive future perspective on reducing malignancies associated with this viral infection, including those affecting the oral cavity and pharynx.

Șerban Vifor Gabriel Berteșteanu1,2, Raluca Grigore1,2, Alexandru Nicolaescu1

1 ENT Head and Neck Surgery Department, General Medicine Faculty, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania

\*Address all correspondence to: alexandru87nicolaescu@gmail.com

2 ENT Head and Neck Surgery Clinic, "Colțea" Clinical Hospital Bucharest,

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\*

survival as well as less morbidity and a better quality of life.

effects of radiation therapy, such as osteoradionecrosis of the mandible, radiomucositis, xerostomia, dental cavities, and teeth avulsion [25]. These have a high impact on the patients' quality of life; thus modern management of HPV-positive oropharyngeal cancer consists in trans-oral excision (with a rising trend towards robotic surgery) of the primary tumor with selective neck dissection followed by low-dose radiation therapy [25].
