**3. Symptoms and diagnosis of NPC**

Due to the concealed anatomical location of NPC, most cases show no specific symptoms at all when the disease is initiated, until they present lymph node metastasis, typically in the neck. Thus, most of the patients missed the opportunity of diagnosis at the early stages.

### **3.1 Symptoms of NPC**

NPC usually occurs in the lateral walls, it grows either within the nasopharynx or extends outward. Being a malignant tumor, NPC can infiltrate or invade surrounding structures, for instance, the base of the skull, the palates, nasal cavity, and the oropharynx. The most common presenting symptom is cervical lymph node enlargement, followed by nasal, aural, and neurological symptoms. Among them, the most noteworthy early symptoms of NPC are the first retracted snot with blood in the morning, which is often overlooked by patients. Enlargement of NPC within the nasopharynx may cause nasal obstructionrelated symptoms, such as congestion, and bleeding. A blockage of the eustachian tube may lead to unilateral tinnitus, hearing loss, and catarrhal otitis media. The brain nerve invasion or skull base bone damage by NPC are often the causes of headaches [28].

#### **3.2 Diagnosis**

The detection of NPC is based on clinical symptoms and physical examination, but a definitive diagnosis requires a biopsy of the lesion. The first choice of the diagnosis of the primary NPC is biopsy under the nasopharynx endoscope [28]. Cervical lymph node biopsy by fine-needle aspiration should only be used when the

#### *Pharynx - Diagnosis and Treatment*

pathological finding in primary tumor biopsy is negative but remains highly suspicious of NPC. Combining with EBV encoded small RNAs (EBERs) *in situ* hybridization examination could help clinical doctors promptly identify the primary lesions [29]. To further assess the tumor size and location, a series of radiologic tests, including computed tomography (CT) scans and magnetic resonance imaging (MRI) of the head and neck are required. This provides additional but necessary information for evaluating the stage of NPC.

Currently, the staging system of NPC is the eighth edition of the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC) TNM Classification, based on the tumor-node-metastasis (TNM) criteria (**Table 1**) [30]. This system is an important guideline for the treatment, as well as the basis for evaluating the treatment outcomes of patients. With the development of imaging techniques and treatment approaches for NPC patients, the TNM classification systems will be significantly refined again. Notably, monitoring plasma EBV DNA and circulating tumor cells (CTC) can further improve the prediction of prognosis [31, 32].


**Table 1.**

*The UICC/AJCC staging system for nasopharyngeal carcinoma (8th edition).*
