**1. Introduction**

Hypopharyngeal carcinoma is relatively rare in all head and neck cancers (approximately 3–5%) [1, 2]. The overall worldwide age-standardized incidence rates occur at a rate of 0.8 per 100,000 (1.4 in men and 0.3 in women) in hypopharyngeal cancer [3]. Bangladesh had the highest incidence with 4.8 per 100,000 [4]. In the past four decades, the incidence of hypopharyngeal cancer has declined smoothly in America, in part due to decreasing intake of tobacco [5–7]. Overall, it is five times greater in males than in females [8] and mainly occurs in the aged 50 to 70 years [5, 9]. However, this tumor rarely occurs at young ages [10].

Epidemiologic studies showed a series of potential environmental risk factors for hypopharyngeal carcinoma development. Tobacco consumption (> 90% of patients) and alcohol abuse (> 70% of patients) are the two well-established risk factors for hypopharyngeal squamous cell carcinoma [11–13]. Heinz Maier et al. reported a time-response correlation between tobacco intake and hypopharyngeal cancer. Besides, the amount of alcohol consumption is also related to cancer development. Compared to non-smokers, it increased the risk by 9.5-fold (adjusted for alcohol consumption) for the long-term smoker (40–60 tobacco years). Also, alcohol drinkers increased the risk of this cancer that was up to 125.2-fold (adjusted for tobacco consumption) for alcoholics (> 100 g/day) [13]. Moreover, there is a synergistic carcinogenic effect between tobacco use and alcohol abuse [14]. Quitting smoking and refrain from drinking may reduce the risks of hypopharyngeal cancer.

Other risk factors, such as nutritional factors, diet, Plummer-Vinson syndrome, gastroesophageal reflux disease [15], and chronic infectious diseases have been reported to increase the risk of hypopharyngeal tumor. An inadequate caloric intake may lead to cancer cachexia, associated with a poor prognosis for hypopharyngeal carcinoma [16]. Plummer-Vinson syndrome is responsible for post-cricoid carcinoma, characterized by dysphagia and iron deficiency anemia [17, 18]. It has been reported that oncogenic viral infection has a close relationship with head and neck cancers. The human papillomavirus (HPV) is involved in the malignant transformation of oropharyngeal carcinoma [7]. Epstein–Barr virus (EBV) infection is relevant to nasopharyngeal carcinoma (NPC) tumorigenesis [19]. Nevertheless, HPV and EBV infection in hypopharyngeal cancer are rare [20–22]. To date, the possible role of HPV in tumorigenesis of hypopharyngeal cancer is still controversial, EBV as well [23, 24].

In hypopharyngeal cancer, most histological types are squamous cell carcinoma (SCC) (up to 95%). That is usually represented poorly differentiated [25]. Adenocarcinoma is less frequent than in hypopharyngeal malignancies, accounted for around 5%. Other rare malignant tumors: papillary (exophytic) squamous cell carcinoma, verrucous carcinoma, and lymphoepithelial-like carcinoma, have been reported. However, the non-epithelial neoplasms that may arise in the hypopharynx include mucosal malignant melanoma, synovial sarcoma, fibrosarcoma, and liposarcoma, are not included [26]. Both histologic confirmations and histopathologic grading of squamous carcinoma should be recorded in hypopharyngeal cancers.

## **2. Symptoms and diagnosis**

#### **2.1 Relevant anatomy of hypopharynx**

There are three parts to the pharynx: nasopharynx, oropharynx, and hypopharynx. As part of the pharynx, the hypopharynx is located behind the entire length of the larynx. It extends from the plane of the epiglottis to the lower border of the cricoid cartilage. Moreover, the pharynx is further classified into three regions (**Figure 1**): (1) the piriform sinuses, (2) the posterior pharyngeal wall, and (3) the post-cricoid area.

The pyriform sinus, a bilateral area, is bounded by the aryepiglottic fold and laterally by the esophagus's upper end. The posterior pharyngeal wall is bounded from the superior level of the epiglottis to the lower border of the cricoid cartilage and from the vertex of one pyriform sinus to the other. The post-cricoid region lies on the arytenoid cartilages' level and connecting to the plane of the inferior border of the cricoid cartilage.

In general, hypopharyngeal cancer occurs most in the piriform sinuses in 60–85% of patients, followed by the posterior pharyngeal wall up to 10–20% and rarely in the post-cricoid area in 5–15% of patients (**Figure 2**) [9, 27]. Also, during these three hypopharyngeal subsites, the tumor of the pyriform sinus and the posterior pharyngeal wall is mainly in males, while post-cricoid carcinoma is more often occurs in females [5, 9].

*Hypopharyngeal Cancer: Staging, Diagnosis, and Therapy DOI: http://dx.doi.org/10.5772/intechopen.97462*

#### **Figure 1.**

*Anatomical subsites of hypopharynx. (A) The pharynx includes three parts: The nasopharynx, oropharynx, and hypopharynx. (B) The hypopharynx is situated posterior to the larynx. It is further subdivided into the pyriform sinuses (left and right), posterior pharyngeal wall, and post-cricoid area.*

#### **2.2 Symptoms and signs of hypopharyngeal carcinoma**

Early in hypopharyngeal cancer is not easy to be found due to the asymptomatic for an extended period. Something sticking or irritative sensation in the throat could be the early symptoms. If the tumor increases to a considerable size, sore throat, increasing dysphagia, and referred otalgia on swallowing may be present. Besides, progressive dysphagia frequently leads to significant weight loss.

A neck mass is now recognized as the typical clinical manifestation of hypopharyngeal carcinoma. There are a rich lymphatic network and vascular anatomy in the neck, allowing tumors to easily metastasize to the cervical nodal. Clinically, more than half of patients have enlarged cervical nodes at initial presentation because of the vibrant lymph nodes network in the pharynx [28]. The neck metastases rate is higher (> 75% of patients) in pyriform sinus cancers, as compared with the neck metastases rate in the posterior pharyngeal wall and post-cricoid cancers [29, 30]. Lymphatics from pyriform sinuses usually result in levels II-III and retropharyngeal node metastasis. And the posterior pharyngeal wall lymphatic metastasis area is more occurred to level II lymph node metastasis. In contrast, lymph node metastasis of the post-cricoid region prefers to levels IV-VI metastasis [31–33].

The larynx functions mainly in airway protection and respiration, which is in front of the hypopharynx. The hypopharynx configuration may allow tumor invasion or involvement of these adjacent organs, for instance, the larynx. When the throat symptoms appear, the tumor is considered significant in particular hoarseness, invading the larynx. Furthermore, some of the patients may present aggressive laryngeal invasion with life-threatening airway obstruction.

#### **2.3 Second primary cancer**

Patients with hypopharyngeal cancer have an exceptionally high risk of diagnosing a synchronous or metachronous second primary cancer, which may be associated with the prognosis's deterioration [34]. One possible mechanism causing second primary cancer in hypopharyngeal cancer is the phenomenon of "field cancerization" [35]. Anatomically, the cervical esophagus is originated at the upper esophageal sphincter, contiguous with the post-cricoid region

#### **Figure 2.**

*Typical subtypes of hypopharyngeal carcinoma. (A, D) The pyriform sinus carcinoma (left) (red arrow) involving the left side of aryepiglottic fold in endoscopy (A) and (D) CT scan. (B, E) The posterior pharyngeal wall carcinoma (red arrow) in endoscopy (B) and (E) CT scan. (C, F) The hypopharyngeal carcinoma (red arrow) arising from the post-cricoid region in endoscopy (C) and (F) CT scan. (G) The patterns of hypopharyngeal carcinoma. (H) The percentages of hypopharyngeal carcinoma in three subtypes.*

and behind the lower border of the cricoid cartilage. The aerodigestive tract mucosa, including hypopharynx and esophagus epithelium, is the squamous epithelium. During the carcinogenesis process, both hypopharynx epithelium and esophagus epithelium are exposed to similar environmental risk factors resulting in multiple cancers in the aerodigestive tract [35–37]. Tobacco use and alcohol abuse are considered as the significant risks contributing to field cancerization.

In head and neck cancers, the overall incidence of the synchronous second primary cancer was estimated to be 12% [38]. However, hypopharyngeal cancer has a high incidence of second primary cancer. The commonest sites in *Hypopharyngeal Cancer: Staging, Diagnosis, and Therapy DOI: http://dx.doi.org/10.5772/intechopen.97462*

#### **Figure 3.**

*The second primary cancer in hypopharyngeal cancer. (A, B) Hypopharyngeal cancer involving pyriform sinus (red arrow) by endoscopy and CT scan, respectively. (C, D) Second primary esophageal cancer of hypopharyngeal cancer, imaged with (C) white light endoscopy; (D) narrow-band imaging.*

the second primary cancer [39] were the esophagus (27%) and lung (6.34%) [40–42]. Therefore, patients with hypopharyngeal carcinoma are suggested to undergo regular surveillance endoscopy (**Figure 3**) and chest CT scan to detect a second malignancy. Precancerous lesions or neoplasm are the targets of surveillance endoscopy. In case of suspected neoplasm, an endoscopic biopsy can be done to diagnose second primary esophageal cancer. The use of narrowband imaging (NBI) shows high accuracy to screen early esophageal lesions, Lugol chromoendoscopy (LCE) endoscopy as well [43]. Most of the second primary cancer followed the hypopharyngeal cancer diagnosis within one year [34, 40].

#### **2.4 Diagnostics of Hypopharyngeal carcinoma**

#### *2.4.1 History and physical examination*

To assess the patient's condition, a thorough history of presenting symptoms must be obtained. It also is crucial to document and quantification of tobacco or alcohol use history. And then, a complete head and neck examination should be performed. Neoplasm and its extent can often be seen on indirect or laryngoscopy

#### *Pharynx - Diagnosis and Treatment*

tests. While the post-cricoid growths may difficult to diagnose on the laryngoscopy. The pooling of secretions in the pyriform sinus is indicated to cervical esophageal involvement. Both sides of the neck should be examined to evaluate cervical lymph nodes, and the level, number, size, and mobility of palpable lymph nodes should be carefully documented.

#### *2.4.2 Endoscopic evaluation and pathology diagnosis*

In early cases, endoscopy of the laryngopharynx is best performed in the patient under suspicion of malignancy. The panendoscopy can evaluate the entire scope of cancer and find a synchronous primary at any other site. A biopsy can be done under general anesthesia with endoscopes. It is essential for histological typing. Since lymphonodi cervical metastasis often occurs as the first symptom, a fineneedle aspiration (FNA) in the neck is recommended.

#### *2.4.3 Imaging studies*

Nowadays, the application of imaging measurement offers an efficient approach for evaluating the tumor extent, lymph nodal staging, potential laryngeal impingement, and cartilage involvement. A CT enhanced scan of the laryngopharynx and neck is exceptionally worthy in evaluating laryngeal cartilage invasion. At the same time, MRI is better for the soft-tissue extension. They are complementary examinations of each other and reveal the tumor invasive range. Due to the distant metastasis (approximately 6% of patients) in hypopharyngeal cancer, a chest CT scan or PET/CT is also recommended [44].

#### **3. Cancer staging and prognosis**

The newly updated TNM classification system (8th edition), an anatomicbased classification, was published in 2017 by The American Joint Committee on Cancer (AJCC). This cancer stage classification aims to provide information for the clinical trial, cancer control activity, therapy selection, and outcome. Compared to the previous version, the new vision reflects a better understanding of cancer therapy and research design. Here we showed an overview of modifications in cancers of pharynx: (1) the revision of TNM classifications in nasopharyngeal cancer; (2) the division of pharyngeal malignancies into HPV-related (p16+) oropharyngeal cancer, oropharynx (p16-) and hypopharynx cancer, and nasopharyngeal cancer; (3) the extranodal extension (ENE) is formulated into the N category for non-viral related head and neck cancer for the first time [45]. Besides, the TNM staging of hypopharyngeal cancer is delineated in **Figures 4** and **5**.

Generally, the cancer of hypopharynx has an abysmal prognosis in all head and neck cancers. Numerous patients (75–80%) are advanced-stage ones (stage III/IV) when initially diagnosed [46, 47]. About 60–75% of patients with cervical lymph node metastasis (N1–3) were detected [46, 47].

A population-based study reported that the five-year overall survival (OS) rate increased from 37.5% (1973–1989) to 41.3% (1990–2003) [9]. Also, Henry T. Hoffman, etc., showed the five-year disease-specific survival segregated into clinical stages increased: 63.1% (stage I), 67.6% (stage II), 41.8% (stage III), and 22% (stage IV), respectively [48]. Although the treatments have improved, the tumor

#### **Figure 4.**

*TNM classification of hypopharyngeal cancer. The TNM staging system is the common language for classifying the extent of spread of cancer. Here we reveal the newest edition in hypopharyngeal carcinoma.*

recurrence within one year and half of first recurrences with distance metastases [1]. Unfortunately, about 50% of the untreated cancer patients surviving within four months after the initial diagnosis, and less than 20% of patients surviving more than one year [49, 50].


**Figure 5.** *Prognostic stage of hypopharyngeal cancer.*
