Nasopharyngeal Cancer

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Continuing Education Activity

Nasopharyngeal carcinoma is a distinct subtype of head and neck cancer. Originating in the nasopharynx, this condition presents unique characteristics that set it apart from other head and neck squamous cell carcinomas. This activity navigates through the World Health Organization's histological classification, addressing the 3 subtypes of nasopharyngeal carcinoma, nasopharynx anatomy, and the fossa of Rosenmulleras the primary subsite of origin. This activity aims to broaden the understanding of nasopharyngeal carcinoma, shedding light on its association with the Epstein-Barr virus and distinguishing it from oropharyngeal cancers linked to other viruses.

Emphasizing the interprofessional approach, this activity underscores the collaborative role of healthcare teams in diagnosing and caring for patients with nasopharyngeal carcinoma. By exploring the unique characteristics of NPC, healthcare professionals are better equipped to collaborate in delivering patient-centered care and optimizing outcomes for individuals affected by this distinct form of head and neck cancer.

Objectives:

  • Identify the distinct histologic features of nasopharyngeal carcinoma through thorough examination and diagnostic tools.

  • Differential nasopharyngeal carcinoma from other head and neck cancers based on specific etiologic factors, geographical risk patterns, and unique disease spread characteristics.

  • Implement tailored treatment plans for nasopharyngeal carcinoma, emphasizing nonsurgical approaches such as radiation therapy and incorporating chemotherapy or immunotherapy based on the disease stage.

  • Coordinate follow-up care and surveillance strategies post-treatment, involving regular physical examinations, nasal endoscopies, and appropriate imaging to monitor disease status and manage potential long-term complications.

Introduction

The pharynx is a tubular structure that connects the nose to the trachea. The upper portion of the pharynx, known as the nasopharynx, is surrounded by various structures. Anteriorly, the posterior choanae of the nasal cavity borders it. Posteriorly, it is enclosed by the mucosa overlying the superior pharyngeal constrictor. Laterally, it is defined by the fossae of Rosenmuller, eustachian tube orifices, and tori tubarius. Superiorly, it is constrained by the sphenoid, and inferiorly, it is connected to the soft palate.

Cancers arising from this area are most commonly squamous cell carcinoma. These cancers may exhibit distinctive behaviors compared to other head and neck squamous cell carcinomas and have unique risk and etiologic factors. The most common subsite of origin is the fossa of Rosenmuller, accounting for 50% of nasopharyngeal carcinomas.[1] 

There are distinct geographic and ethnic risk factors for nasopharyngeal carcinoma. In Asia, mainly China, there is a high incidence of disease. Having Chinese ancestry is an independent risk factor regardless of residence location.[2] A high incidence of nasopharyngeal cancer has also been noted in those of Native Alaskan ancestry.[3]

Most cases in areas with a high disease incidence are related to Epstein-Barr virus (EBV) infection. However, the near-ubiquity of EBV in the global population makes specific viral etiologic pathways challenging to understand.[4] Viral oncogenes LMP-1, LMP-2, and EBNA1 have been demonstrated to play an important role.[5] Although human papillomavirus (HPV)-related nasopharyngeal cancers have also been reported, no clear association has been established.

The clinical behavior of nasopharyngeal cancers varies depending on their histological subtype. The World Health Organization (WHO) has classified nasopharyngeal carcinoma into 3 subtypes based on histology. Type 1 is keratinizing squamous cell carcinoma, associated with EBV infection in around 70% to 80% of cases.[6] Type 2 is differentiated nonkeratinizing carcinoma, and type 3 is undifferentiated carcinoma, the most common subtype of nasopharyngeal cancer.[7] The latter 2 types are also most responsive to treatment. Almost all cases of type 2 and type 3 are related to EBV and occur in areas where EBV is endemic. Nasopharyngeal cancer with basaloid features is a newer, rarer histologic category known to behave aggressively.[8] 

Treatment is determined based on stage and is typically nonsurgical owing to technical reasons. Radiation therapy may be used alone for early (stage I and II) disease, while chemotherapy may be added for stage III or IV disease. Genetic markers, including some viral-related surface proteins, may also be used as targets for immunotherapy.[9] 

Over the past decade, mortality related to nasopharyngeal cancers has seen improvement attributed to early detection and advances in treatment.[10][11][12] This progress underscores the importance of ongoing research and innovations in nasopharyngeal cancer management.

Etiology

The precise etiology of nasopharyngeal carcinoma is complex and not fully understood. Carcinogenesis is most likely due to hereditary genetics, environmental factors, and viral factors. In areas where EBV is not endemic, such as the US, smoking and alcohol have been identified as risk factors for nasopharyngeal carcinoma. Conversely, in EBV-endemic areas, this association does not hold.[13] This difference is reflected by WHO type 1 tumors, which are more variable in etiology and unrelated to EBV. In comparison, the association between EBV and WHO type 2 and 3 tumors is definitive.[14] 

Other risk factors include Asian ancestry, particularly Chinese ancestry, remaining an independent risk factor even outside of Asia.[15] This theory explains the increased nasopharyngeal carcinoma risk in those of Native Alaskan ancestry, as common ancestral genetic links have been described utilizing D4h mitochondrial DNA analysis.[16] Dietary risk factors, such as diets high in preserved foods containing nitrosamines (particularly salted preserved fish), have also been postulated to confer additional risk of nasopharyngeal carcinoma.[17] 

Some epidemiologic studies establish family clusters of nasopharyngeal cancer in endemic and nonendemic areas, suggesting ancestral genetics and environmental factors likely play an etiologic role.[18][19] In some endemic areas worldwide, circulating EBV DNA is utilized for screening and disease surveillance. High circulating levels of EBV DNA are associated with poorer treatment response and higher rates of distant metastasis and mortality.[20] The prognostic value of circulating EBV titers has not been extensively studied, but persistently elevated EBV titers after treatment have been described as a powerful poor prognostic factor for overall survival.[21][22]

Epidemiology

There are significant geographic variations in the epidemiology of nasopharyngeal carcinoma. In nonendemic areas, such as the Americas and Europe, nasopharyngeal cancer is rare, with less than 1 case per 100,000 people.[23] The incidence is much higher, reaching up to 21 cases per 100,000 people in certain parts of China, where nasopharyngeal carcinoma accounts for 18% of all cancers.[24] In Asia, nasopharyngeal carcinoma is a disease of middle age, with patients presenting in the 4th through 6th decades of life.[25] In Africa, another area with endemic EBV infection, the majority of cases are observed in children.[26][27] 

Nonendemic areas regions, such as the Americas and Europe, exhibit a bimodal age distribution. The first peak occurs in the late teenage years, and the second peak appears in the sixth to seventh decade of life.[28] Gender discrepancies exist in the risk of developing nasopharyngeal carcinoma and in nasopharyngeal carcinoma-specific mortality. Males are traditionally reported to have a 2.75-fold higher risk of developing nasopharyngeal carcinoma and a 3.25-fold greater risk of dying from nasopharyngeal carcinoma compared to females.[29] It remains unclear whether this additional risk and mortality are related to differing tobacco use patterns among men and women, and much of the data originates from China. In this endemic area, tobacco smoking is much more common among men than women. Some of these discrepancies have also been age-dependent, with risk and mortality nearly equivalent in those over 55 years in one Chinese study.[30]

Pathophysiology

Nasopharyngeal carcinoma stands out as a distinct subtype of head and neck cancer with a pathogenesis that is equally unique. Most nasopharyngeal carcinoma cases are EBV-related, and research regarding pathogenesis and malignant transformation in nasopharyngeal carcinoma has focused on various viral gene products, along with host genetic factors that may increase susceptibility to EBV infection.[31]

In endemic areas, the majority of nasopharyngeal carcinoma tumor cells and precancerous lesions have been found to contain isolated EBV DNA, reinforcing causative association. Additionally, a strong correlation exists with human leukocyte antigen (HLA) mutations that increase susceptibility to malignant transformation, and these mutations are more prevalent among individuals of Chinese and other Southeast Asian ancestries.[32] The most potent risk factors for nasopharyngeal carcinoma development have been identified as major histocompatibility complex (MHC) I gene variants.[33]

The most widely accepted theory of tumorigenesis in EBV-related nasopharyngeal carcinoma (given EBV's implication in various malignancies) suggests a clonal malignancy originating from a single, latently infected progenitor cell in the lymphocyte-rich nasopharyngeal mucosa.[34] A hallmark of EBV-related nasopharyngeal carcinoma is the necessity for multiple genetic abnormalities induced by latent viral genes for oncogenesis. Specifically, EBNA, EBER1, and EBER2 have been extensively studied,[35][36] with LMP1 emerging as a key oncoprotein. LMP1 is a potent signal activator for various pathways, including JNK/AP1, P13K, MAPK, and NF-κB.[37][38]

Histopathology

Nasopharyngeal carcinoma exhibits distinctive histopathological features. The WHO classifies nasopharyngeal carcinoma into 3 main subtypes based on histology:

Type 1. Keratinizing: Histologically indistinguishable from keratinizing squamous cell carcinoma in other body sites. It exhibits apparent squamous differentiation with prominent intracellular bridges and variable keratinization, including keratin pearls. Consequently, it can be graded as well, moderate, or poorly differentiated based on the degree of keratinization.[39]

Type 2. Nonkeratinizing (differentiated): Characterized by cords or trabeculae of interconnected cells with well-defined borders and little to no keratinization. The presence or absence of intracellular bridges may vary, and the tumor may exhibit a resemblance to urothelial carcinoma. Typically, there is no desmoplastic response to the cancer, although the stroma may display a nonneoplastic lymphoplasmacytic infiltrate.

Within the same tumor, there may exist both differentiated and nondifferentiated loci. The classification of the tumor should be according to the dominant component. This classification of degree of differentiation is optional, as it does not carry any prognostic significance.

Type 3. Nonkeratinizing (undifferentiated): Displays 1 of 2 predominant patterns on hematoxylin and eosin (H&E) staining, though these patterns do not appear to affect prognosis:[40]

  • Regaud pattern: Cohesive cells with indistinct margins arranged in a syncytial pattern
  • Schmincke pattern: Noncohesive cells with a diffuse cellular infiltrate, resembling non-Hodgkin lymphoma

The cells in this subtype typically exhibit round nuclei with prominent nucleoli. There is an absence of keratinization, while increased mitoses and apoptosis are universally present. However, necrosis is infrequent. Additionally, a nonneoplastic lymphoplasmacytic infiltrate is often observed in the surrounding tissue.

Immunohistochemistry is crucial in characterizing nasopharyngeal carcinoma by detecting specific protein markers. Positive staining is observed for the following markers in nasopharyngeal carcinoma:[41]

  • EBV latent membrane Protein
  • High molecular weight keratin
  • Pancytokeratin
  • p63
  • p40

Negative staining is noted for the following markers:

  • CK20
  • CD45
  • S100
  • HMB45
  • MelanA
  • Desmin
  • Myoglobin
  • Myogenin
  • CK7 (may occasionally show positivity)

EBV DNA is detected in 75% to 100% of nasopharyngeal carcinoma cases using PCR or FISH.[42] This high detection rate underscores the significance of EBV DNA testing in confirming the presence of EBV in nasopharyngeal carcinoma, aiding in accurate diagnosis and treatment planning.

History and Physical

Symptoms of nasopharyngeal cancer are stage-dependent, and most cases present at an advanced stage with a palpable neck nodal metastasis.[43] A solitary, painless, incidentally noted neck mass is a common initial sign and symptom in various head and neck cancers. In adults, a new neck mass that has persisted for over 2 weeks should be presumed malignant until proven otherwise. Inquiry into the onset of the neck mass, its identification method, and any antecedent upper respiratory or dental infections are crucial. Additionally, changes in the mass size and the presence of any other neck masses should be addressed.

Associated symptoms such as hoarseness or voice changes, dysphagia or odynophagia, otalgia, nasal obstruction (unilateral versus bilateral), epistaxis, hemoptysis, hematemesis, vision changes, headache or facial pain, and persistent rhinorrhea should be carefully investigated. Gathering a comprehensive social history, including information on tobacco and alcohol use, prolonged sun exposure (occupational or recreational), sunscreen use, and occupational history, is essential. Family and ethnic background, particularly in individuals of Asian ancestry, should be obtained. A thorough past medical history, including any previous head and neck cancers, skin cancers, or immunosuppression, should also be documented.

A comprehensive physical examination of the head and neck is imperative. The skin and scalp should be examined for visible or palpable lesions, and investigation into encountered scars is essential to determine whether they represent previously excised malignant or premalignant lesions.

The otologic examination is necessary to assess the middle ears for effusion, with particular attention to unilateral effusion, as it may indicate nasopharyngeal obstruction in adults. Anterior rhinoscopy is crucial for detecting visible lesions before and after administering topical decongestant. Nasal endoscopy is essential for a thorough evaluation of the nasopharynx. While some adenoid tissue may persist into adulthood, the presence of prominent or asymmetric adenoids in adults is a cause for concern.

An oral cavity and oropharyngeal examination should focus on mucosal lesions, dental health, and palpation of the tongue, base of the tongue, and floor of the mouth. Flexible laryngoscopy is necessary to examine the tongue base, oropharynx, and hypopharynx thoroughly. Any masses or lymphadenopathy, thyroid nodules, and stridor or hoarseness should be carefully noted during the neck examination. A cranial nerve examination is mandatory, particularly in identifying deficits or asymmetries.

Evaluation

A thorough history and physical examination of the head and neck are paramount, guiding all subsequent workups. If a suspicious mass is identified in the oral cavity, oropharynx, thyroid, or hypopharynx, a computed tomography (CT) scan with intravenous (IV) contrast of the neck should be obtained.  

The choice of subsequent imaging for a suspicious mass in the nasopharynx has been historically controversial. CT with IV contrast has long been the preferred imaging modality for initial staging. CT excels in determining bony invasion and evaluating the relevant nodal basins and is often required for treatment planning in radiation therapy.[44] However, CT is less accurate in assessing the extent of soft-tissue involvement, and its resolution may be inadequate for detecting extremely small tumors, where magnetic resonance imaging (MRI) or positron emission tomography and CT (PET-CT) can be more helpful, respectively.[45] 

Practical and logistical considerations may lead to obtaining a CT scan as the first-line imaging modality today, especially where CT is more widely available or required for insurance reasons. CT is also chosen when patients are unable to undergo an MRI due to implanted metal or claustrophobia. In cases where CT is used, obtaining fine-cut (1 to 2mm) images through the nasopharynx is crucial for optimal evaluation of the presumed tumor and the neural foramina of the skull base.[46] 

MRI of the face and neck is the best modality for evaluating the extent of the primary tumor (T stage) with the utmost precision. It surpasses other imaging techniques in detecting subclinical primary tumors that might be missed on endoscopy and CT scans.[47] While CT scans also effectively assess cervical lymph nodes, MRI is considered an acceptable alternative.[48] However, a PET scan is strongly recommended for evaluating metastatic disease (M stage) due to the tendency of nasopharyngeal cancers to metastasize, as well as its capability to identify subclinical nodal metastases.

A histologic diagnosis is essential for accurate staging and treatment planning. This can be effectively achieved through an endoscopic biopsy of a nasopharyngeal mass performed under local or general anesthesia. In cases where the primary tumor is not readily evident clinically, fine needle aspiration of the metastatic neck node can be conducted for cytology and EBV testing. An EBV-positive nodal metastasis can be safely assumed to originate from a nasopharyngeal primary, facilitating staging, prognosis, and treatment decisions, even without a visible primary lesion.[49][50][51] 

The standard of care for these patients involves an interprofessional evaluation, typically conducted in a tumor board or another multidisciplinary clinic. This collaborative approach includes consultation with medical oncology, radiation oncology, surgical oncology, radiology, and pathology.

Treatment / Management

Nonsurgical approaches are the primary mode of treatment for most nasopharyngeal cancers. The anatomical challenges posed by the nasopharynx make surgical access difficult, and the typical late-stage presentation of nasopharyngeal carcinoma often renders primary tumors unresectable due to the involvement of bony structures that cannot be safely removed. Although exceptionally rare, small primary nasopharyngeal carcinoma cases may be considered for surgical treatment using endoscopic or transpalatal approaches, primarily documented in case-series reports.[52] 

In instances of local failure after primary chemo and radiation therapy, nasopharyngectomy (either endoscopic or open) has been employed. Notably, the most extensive series reported more than 80% local control at 2 years postoperatively.[53] However, it is essential to recognize that surgical intervention in nasopharyngeal cancer remains a specialized and infrequently utilized option.

Nonsurgical treatment for nasopharyngeal carcinoma includes radiation therapy, chemotherapy, or a combination of modalities, depending on the stage of the tumor. Efforts should be made to enroll all patients in available clinical trials to explore innovative and potentially more effective treatment approaches.[9]

Radiation Therapy

Radiation therapy is the essential treatment modality for nasopharyngeal carcinoma. The introduction of intensity-modulated radiation therapy in the 1990s has established a new standard of care. Consensus guidelines for tumor delineation in nasopharyngeal carcinoma have been established to optimize oncologic control while minimizing toxicity to critical surrounding structures such as the eyes, brain, middle ear, and temporomandibular joint.[54] In stage I nasopharyngeal carcinoma, radiation therapy is used as a single-modality treatment, and chemotherapy is added for more advanced-stage disease, as discussed later.

Traditionally, treatment fields for nasopharyngeal carcinoma encompassed the entire (bilateral) nasopharynx, along with the at-risk nodal basins of the retropharynx and bilateral neck. The fossa of Rosenmuller is the most common site of origin within the nasopharynx, representing over 80% of nasopharyngeal carcinoma cases, with the tumor remaining unilateral in up to 90% of cases even as the tumor expands.[55][56] Recognizing the potential to reduce radiation dose volumes, the deliberate exclusion of the contralateral nasopharynx and surrounding critical structures in the NRG HN001 trial resulted in up to 62% reduction in CTV2 volume and a decreased dose to multiple critical structures by up to 33%.[57]

Nasopharyngeal carcinoma presents a high risk of nodal metastasis, often being the primary complaint at the time of diagnosis. Except for stage I disease, the at-risk nodal basins must be treated. While the level II (jugulodigastric) nodes were traditionally considered the most frequent site of metastasis in nasopharyngeal carcinoma, modern imaging techniques have identified retropharyngeal nodes as the most common metastatic site.[58] Nodal metastatic progression typically follows a stepwise pattern: first, the retropharyngeal notes, then proceeding caudally along the deep cervical nodes to levels III, IV, and V. Level I, the intraparotid nodes, supraclavicular nodes, and level VI were found to be highly low-risk basins in a meta-analysis of over 10,000 nodes.[59] 

An important caveat relates to level Ib. Sparing the submandibular glands to minimize xerostomia is often desirable, mainly if level I is low-risk. If the level II nodes are greater than 2 cm or display extracapsular spread, the level Ib nodes are considered higher risk and should be included in the treatment fields.[60] Current international guidelines recommend a total dose of 70 Gy to high-risk clinical target volume and 50 to 60 Gy to low- and intermediate-risk clinical target volume.[51] 

In cases of treatment failures, most local failures occurred within the high-dose fields, prompting interest in de-escalation to reduce radiation therapy-associated morbidity to surrounding structures.[61] This is an area of active research, with trials demonstrating encouraging short-term results after gradient dosing in dose prescription, as opposed to the more traditional 2-tiered dosing.[62] Induction chemotherapy has also been employed as a method to identify tumors responsive to de-escalation, especially in the pediatric population, where the long-term consequences of facial radiation are significant. Promising results have been reported in clinical trials, such as the NPC-2003-GPOH/DCOG trial, using various induction chemotherapy protocols for de-escalation, with 5-year, event-free survival rates of 77% to 91% reported after de-escalation to 45-68 Gy.[63]

Chemotherapy

A phase III intergroup study demonstrated a statistically significant improvement in progression-free survival and overall survival for patients with stage III and locally advanced stage IV nasopharyngeal carcinoma when treated with bimodality therapy comprising radiation therapy with systemic chemotherapy.[64][65][66] These early studies have formed the foundation of current international treatment guidelines for advanced-stage nasopharyngeal carcinoma. The most current international recommendations, jointly issued by the American Society of Clinical Oncology and the Chinese Society of Clinical Oncology, advocate the following approaches:

  • For patients with stage II disease, the role of chemotherapy depends on the status of the lymph nodes.
  • In T2N0 disease, chemotherapy is not routinely offered.
  • In T1-2N1 disease, concurrent chemoradiation therapy is recommended.
  • For patients with T3N0 disease, concurrent chemoradiation therapy is recommended, and induction chemotherapy or adjuvant chemotherapy may be offered.
  • For patients with all other stage III-IVA disease, concurrent chemoradiation therapy should be administered, along with either induction or adjuvant chemotherapy.[67]

Concurrent chemotherapeutic for nasopharyngeal carcinoma typically involves the use of cisplatin, which remains the agent of choice. The administration of cisplatin varies as follows:

  • Patients without contraindications, cisplatin is ideally administered concurrently with radiation therapy as follows:[68][69][70][71][72] 
    • Weekly 40 mg/m2 for 7 doses or,
    • Tri-weekly 100 mg/m2 for 3 doses
  • Patients with contraindications to cisplatin may use the following treatment options:[67] 
    • Carboplatin AUC5-6 triweekly
    • Nedaplatin 100 mg/m2 triweekly
    • Oxaliplatin 70 mg/m2 
  • If a patient cannot tolerate any platinum-based chemotherapy, concurrent use of capecitabine, tegafur, and 5-fluorouracil (5-FU) radiation therapy is also an option.[73]

Induction chemotherapeutic agents:

Platinum-based agents are recommended for all patients undergoing induction chemotherapy, with a notable increase in overall survival documented in a landmark phase II study in 2009. This study showed an improvement in overall survival from 68% to 94% with the addition of 2 cycles of docetaxel.[74] Current recommended induction regimens include:[75][76][77][78]

  • Docetaxel 60 to 75 mg/m2 on day 1; cisplatin 60 to 75 mg/m2 on day 1; 5-FU 600 to 750 mg/m2 per day, continuous infusion on days 1 to 5
  • Gemcitabine 1000 mg/m2 on day 1 and day 8; cisplatin 80 mg/m2 on day 1
  • Cisplatin 80 to 100mg/m2  on day 1; 5-FU 800 to 1000 mg/m2 per day, continuous infusion on days 1 to 5
  • Cisplatin 100 mg/m2 on day 1; capecitabine 2000 mg/m2 per day on days 1 to 14
  • Docetaxel 75 mg/m2 on day 1; cisplatin 75mg/m2 on day 1.

Adjuvant chemotherapeutic agents:

Platinum-based agents are essential in all patients receiving adjuvant chemotherapy for nasopharyngeal carcinoma unless contraindicated.[68] The preferred regimen is:

  • Cisplatin 80 mg/m2 on day 1 or 20 mg/m2 on days 1 to 5; 5-FU 1000 mg/m2 per day, continuous infusion on days 1 to 4 or 800 mg/m2 per day, continuous infusion on days 1 to 5. This is to be administered every 4 weeks for 3 cycles.[79][71] 
  • Carboplatin may be used if cisplatin is intolerable and can be combined with 5-FU.[80] Enrolling in a clinical trial is recommended, if possible, in the presence of a significant contraindication to platinum-based agents. Nonplatinum-based agents in nasopharyngeal treatment remain experimental and should not be routinely offered.[67]

Differential Diagnosis

Several conditions may present with symptoms similar to nasopharyngeal carcinoma, making differential diagnosis crucial. Some of the conditions to consider include:

  • Enlarged adenoids/HIV-associated lymphatic hyperplasia
  • Antrochoanal polyp
  • Inverting  papilloma
  • Vascular malformation
  • Malignancy
  • Nasal polyposis
  • Infectious mononucleosis
  • Non-Hodgkin lymphoma
  • Sarcoma
  • Adenocarcinoma
  • Wegener granulomatosis
  • Rhinosporidiosis

Prognosis

The prognosis of nasopharyngeal carcinoma is closely linked to its stage at presentation. A more favorable survival outcome is observed in stage I disease, whereas stage IV disease is associated with the poorest prognosis. The overall relative 5-year survival rate for stage I nasopharyngeal carcinoma is 82%. However, for stage II disease, this rate decreases to 72%, and in the case of stage IV disease, the 5-year relative survival rate drops further to 49%[81][82].

After initial treatment, patients should maintain regular follow-ups with their oncologist for cancer surveillance. This involves physical examinations, nasal endoscopy, and possibly serum labwork for EBV DNA and thyroid function due to the risk of post-radiotherapy hypothyroidism. Detectable EBV DNA levels post-treatment are associated with an unfavorable prognosis, making it an established negative prognostic marker for nasopharyngeal carcinoma.[83] However, the use of circulating EBV DNA in monitoring after chemoradiotherapy for nasopharyngeal carcinoma remains under investigation.[84] 

Currently, the standard of care for posttreatment surveillance includes physical examination and nasal endoscopy, with the optimal timeline and frequency being a subject of debate. Many experts recommend frequent screening in the first 12 to 24 months post-treatment, such as every 3 months. This may be extended to every 4 to 6 months during years 3 to 5 post-treatment and annually after that.[85] 

Most centers conduct a posttreatment PET-CT scan 3 months after completing radiotherapy, followed by a 1-year posttreatment PET-CT if the initial scan is normal.[86]  If both scans are negative, further surveillance imaging may not be recommended in nonendemic areas.[87][88] However, these guidelines may vary, and individualized approaches may be considered based on patient-specific factors and evolving research.

Complications

Nasopharyngeal carcinoma and its treatment can lead to various complications. Here are some potential complications associated with nasopharyngeal carcinoma:

Treatment-Related Complications

  • Radiation therapy adverse effects: Radiation therapy can cause adverse effects such as mucositis, xerostomia (dry mouth), radiation dermatitis, and fatigue.
  • Chemotherapy adverse effects: Chemotherapy may lead to nausea, vomiting, fatigue, hair loss, and increased susceptibility to infections.
  • Immunosuppression: Cancer and its treatments can weaken the immune system, making individuals more susceptible to infections.

Long-Term Adverse Effects

  • Xerostomia: A dry mouth due to reduced salivary gland function, often caused by radiation therapy, can lead to difficulties in swallowing and speaking and an increased risk of dental issues.
  • Hearing loss: Depending on the location and extent of the tumor, hearing loss may occur, primarily if the cancer affects the nearby structures.
  • Cognitive issues: Radiation therapy to the head and neck region may affect cognitive function.

Metastasis and Recurrence

  • Distant metastasis: Nasopharyngeal carcinoma has a propensity to metastasize to distant organs.
  • Local recurrence: Despite treatment, local tumor recurrence may occur, necessitating further interventions.

Secondary Cancers

  • Treatment-related secondary cancers: Long-term survivors of nasopharyngeal carcinoma may be at a higher risk of developing secondary cancers, often related to the treatment received.

Deterrence and Patient Education

Deterrence and patient education for nasopharyngeal carcinoma encompasses a range of strategies aimed at preventing the development of the disease and informing individuals about various aspects related to nasopharyngeal carcinoma. Education efforts emphasize key risk factors, such as EBV infection, family history, and geographic predispositions, encouraging individuals to avoid known risk factors like tobacco use and excessive alcohol consumption.

Lifestyle modifications, including a healthy diet and regular physical activity, are promoted for risk reduction. Emphasis is placed on the significance of early detection through regular health check-ups and screenings, with information about nasopharyngeal carcinoma symptoms provided to the public. Considering the increased risk in specific regions and among certain ethnic groups, education addresses geographic and ethnic considerations, urging vigilance and prompt medical attention in high-risk populations.

Awareness about EBV infection and hygiene practices to reduce transmission is highlighted, alongside genetic counseling services for those with a family history of nasopharyngeal carcinoma. Encouraging regular health check-ups and providing information on available treatment options, potential adverse effects, and prognosis are integral aspects.

Pearls and Other Issues

Key facts to keep in mind about nasopharyngeal carcinoma are as follows:

  • Nasopharyngeal carcinoma has a distinct geographic distribution, with a higher incidence in Southeast Asia, particularly in regions like China.
  • EBV infection is strongly associated with nasopharyngeal carcinoma, especially in endemic areas.
  • Genetic factors, family history, and environmental exposures, such as consumption of preserved foods containing nitrosamines, are implicated.
  • Smoking and alcohol use may be risk factors in nonendemic areas.
  • Nasopharyngeal carcinoma is classified into 3 histological subtypes by the WHO: keratinizing squamous cell carcinoma (Type 1), differentiated nonkeratinizing carcinoma (Type 2), and undifferentiated carcinoma (Type 3).
  • Symptoms may include a painless neck mass, otitis media, nasal obstruction, and other head and neck-related symptoms.
  • Diagnosis often occurs at an advanced stage due to the anatomical location of the nasopharynx.
  • Diagnosis is confirmed through biopsy, often via endoscopic procedures.
  • Imaging studies such as CT and MRI are used for staging and treatment planning.
  • EBV DNA testing may be utilized for screening and monitoring.
  • Chemotherapy is often used in combination with radiation for more advanced stages.
  • Surgery is rarely employed due to the challenging anatomical location of the nasopharynx.
  • Prognosis is stage-dependent, with Stage I having a more favorable outlook compared to Stage IV.

Enhancing Healthcare Team Outcomes

Collaboration among healthcare professionals is paramount in providing comprehensive, patient-centered care for nasopharyngeal carcinoma. Physicians and advanced practitioners should demonstrate proficiency in diagnosis, staging, and treatment planning, incorporating surgical skills and expertise in chemotherapy or immunotherapy. Nurses are vital in supportive care, symptom management, and patient education, while pharmacists ensure safe medication administration.

Regular interdisciplinary tumor board meetings facilitate collective decision-making, while an ethical approach involves informed consent and cultural competence. Effective interprofessional communication is maintained through regular team meetings and clear patient handovers, and care coordination involves patient navigation services and post-treatment follow-up plans. This collaborative approach optimizes patient outcomes, enhances safety, and improves the quality of care for individuals with nasopharyngeal carcinoma.

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Shreya Sinha

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Ryan Winters

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Ajeet Gajra

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2/3/2024 12:10:45 PM

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References

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