The Link Between Adenoids and Nasopharyngeal Carcinoma

Chapter The Link between Adenoids and Nasopharyngeal Carcinoma Du-Bois Asante, Patrick Kafui Akakpo and Gideon Akuamoah Wiafe Abstract Adenoids, play a significant role in inflammatory response, especially in children. Together with other tissues of the lymphatic system, it fights off infections. In most cases of nasopharyngeal cancer, though rare, other histopathological variants of adenoids are seen. Adenoid hypertrophy is mostly observed, which causes obstruction of the nasopharynx and dysfunction of the Eustachian tube because of the formation of an abnormal tissue mass. Different viral and bacterial pathogens are associated with adenoid hypertrophy, including Epstein-Barr virus (EBV), coronavirus, parainfluenza virus, Mycoplasma pneumoniae, Staphylococcus aureus, and Neisseria gonorrhoeae. Among these, EBV is associated with both adenoid hypertrophy and nasopharyngeal cancer, indicating the effect of EBV on both nasopharyngeal cancer and adenoids. We critically appraise the current evidence and discuss potential link between adenoids and nasopharyngeal carcinoma. Keywords: adenoids, nasopharyngeal carcinoma, Epstein-Barr virus, adenoid hypertrophy, nasopharynx, lymphoid tissue 1. Introduction Adenoids also known as nasopharyngeal tonsils, is a collection of lymphoid tissue found on the level of the soft palate, at the posterior wall of the nasopharynx. At this site, the introduction of antigens through the nasal and oral cavities, are detected by the lymphocytes in the Waldeyer’s ring [1]. This results in the priming of the infant’s immune system, ultimately contributing further towards immunologic memory and production of antibodies in children. Adenoids are present at birth and enlarge to a maximum size usually in children, after which adenoidal tissue atrophy occurs. They are nearly absent during adulthood. Thus, adenoiditis is commonly a disease diagnosed during childhood and adolescence. Adenoiditis or hypertrophic adenoids occurs when there is inflammation of the adenoid tissue resulting from infection, allergies, or irritation from acid chyme reflux. In adults, they may be as a result of compromised immunity. Persistence of the etiological agents may lead to adenoid hypertrophy, which is responsible for many of the complications of adenoid disease, including Eustachian tube dysfunction and recurrent acute otitis media [2]. Malignant forms of adenoids are called adenoid cyst 1 Tonsils and Adenoids carcinoma, and though rare (about 1% of all carcinomas of the head and neck), they are locally aggressive and show perineural invasion [3]. Nasopharyngeal carcinoma (NPC) on the other hand, is classified as a malignant neoplasm, arising from the mucosal epithelium of the nasopharynx, most often within the lateral nasopharyngeal recess or fossa of Rosenmüller [4]. Unlike other cancer types that are primarily linked with the aged, NPC can also be seen in children [5] and young patients [6]. In South China (where NPC is an epidemic disease), hypertrophic adenoids and NPC are commonly diagnosed together, mainly in young individuals [7]. Similarly, EBV as an aetiological agent, is a commoner of both adenoids [8, 9] and NPCs [10]. Hence, due to their anatomical location, a common aetiological agent, these two lesions, in some cases are commonly diagnosed together in the ear, nose and throat (ENT) departments of hospitals and also coexist in young individuals. Differentiating these two from each other during treatment could prevent overdosage and measurement of potentially false tumour size. And this is crucial, as response to therapy by these two lesions are different [11]. In recent years, multiple studies have been carried out on adenoids and NPC separately, but few have looked at their coexistence in a patient. Thus, we carried out a literature search in NCBI PubMed using ‘Adenoids’ together with ‘Nasopharyngeal carcinoma’ as single entities or together. We summarized the findings of these studies and discuss potential link between adenoids and nasopharyngeal carcinoma. 2. Adenoids Adenoids develop from week 6 of gestation [12], and are described as lymphatic tissue mass lining the roof and posterior superior wall of the nasopharynx [12, 13]. Adenoids form a larger part of the lymphatic tissue of the Waldeyer’s ring comprising palatine, pharyngeal and lingual tonsils. These tonsils constitute the mucosa-associated lymphoid tissue (MALT) [1, 13, 14] and specifically function as an important part of the immune system early in human life. The Waldeyer’s ring is named after a twentieth-century German anatomist, Heinrich Wilhelm Gottfried von WaldeyerHartz. Blood supply to the adenoids is by the ascending pharyngeal artery, ascending palatine artery, the tonsillar branch of the facial artery, the pharyngeal branch of the maxillary artery, artery of the pterygoid and the basisphenoid artery. Venous drainage is via the pharyngeal venous plexuses through the paratonsillar veins to the facial and internal jugular veins. The lymphatic drainage of the adenoids is directed via the retropharyngeal and pharyngomaxillary lymph nodes [15]. Adenoids act as the first site of defense against infectious agents and inhaled allergens in the nasopharynx. With their ciliated epithelial lining, they sample pathogens and generate immune responses against them. This sometimes leads to the development of immunologic memory which persists throughout childhood. Adenoids are relatively small at birth, grow and peak in size around age 10. They gradually atrophy in adolescents to late adulthood [16, 17]. The hypertrophy of adenoids observed in children around age 6–10 is physiologically normal. However, these hypertrophied adenoids in children and adults are commonly linked to chronic infections, and sometimes allergies [18]. Since adenoids are largely seen in children, adenoid hypertrophy (AH) is more present in children than in adults, with 34.46% prevalence in children and adolescents [19]. AH causes a blockage in the airflow 2 The Link between Adenoids and Nasopharyngeal Carcinoma DOI: http://dx.doi.org/10.5772/intechopen.1001347 through the nasopharynx forcing affected individuals to breathe through the mouth. This results in difficulties in feeding, sleeping and speech [20, 21]. Otitis media (resulting from the obstruction of the orifice of the eustachian tube), cranial facies, chronic rhinosinusitis, snoring, cough, restlessness and attention deficits are among the observed symptoms that result from AH. Hypoxia and hypercarbia are also seen in extreme cases [18, 22–24]. Persistent untreated hypertrophy of adenoids exacerbates infections and reduces immunity which may lead to the development of other infection induced complications [25]. Overall, its anatomical position in the region of the nasopharynx exposes it to many and variety of microorganisms and allergens, making it an ever-active first line immunological ground. 3. Nasopharyngeal cancer NPC is a malignant squamous cell carcinoma that originates in the nasopharynx (specifically the pharyngeal recess, thus the fossa of Rosenmüller). Though uncommon in most part of the world, it is geographically endemic in populations of Southern China, Southeast Asia, the Artic, some parts of North Africa and the Middle-East [26–29]. Out of the 129,079 cases of NPC reported globally in 2018 by the International Agency for Research on Cancer, Asia recorded over 85% of the reported cases. Over 72,000 mortality cases were recorded with only China accounting for 40.14% [26, 30–32]. Reports indicate that NPC disproportionately affects males than females [26, 29, 33, 34]. Studies conducted in North America revealed a higher incidence of NPC among migrated Asian population as compared to resident Caucasians, suggesting a genetic predisposition to the occurrence of the carcinoma [35–37]. Histologically, the World Health Organization (WHO) classifies NPC into three major forms: type I-keratinizing squamous cell carcinoma (SCC), type II-nonkeratinizing differentiated squamous cell carcinoma and type III-non-keratinizing undifferentiated squamous cell carcinoma. A rare variant, basaloid SCC has also been identified [26, 28, 37]. Type I is more common in other parts of the world whereas Type II and III are mostly seen in NPC cases from endemic areas [38]. 4. Anatomical and pathological relationship between adenoids and nasopharyngeal cancer Due to their location, both AH and NPC have the potential to cause obstruction of the orifice of the Eustachian tubes leading to serous otitis media and middle ear infections [39, 40]. This can potentially progress [41, 42] leading to hearing loss and speech problems. AH has the ability to expand into the posterior choanae and cover significant sections of the nasopharynx, obstructing airflow and causing mouth breathing [43]. In 2014, a retrospective study conducted by Berkiten et al. reported that 82.95% of (over 1600 individuals) patients had undifferentiated NPC with nasal obstruction as the common symptom. Interestingly, the study also concluded that hypertrophic adenoids are the major cause of nasal obstruction observed in these adult patients [44]. And this aforementioned condition is also common in children [45]. The abnormal inflammation of the adenoid presents an environment for the potential development of NPC since unresolved proliferation of the adenoidal lymphoid tissue reduces immunity at the nasopharyngeal region, allowing for recurrent infections as seen in EBV reported cases. 3 Condition (NPC/ Adenoid) Causative agent(s) identified Histotype present Observed symptoms Technique used Treatment option Age range (years) References 1 AH NR NR NR Lateral neck X-ray NR 5–14 Moideen et al. [23] 2 AH Human herpesviruses 6, cytomegalovirus, EBV NR NR Quantitative realtime PCR NR 2–11 Lomaeva et al. [47] 3 AH NR NR NR Lateral cephalogram NR 6–11 Zhao et al. [24] 4 AH NR NR NR Lateral soft tissue neck X-ray Adenoidectomy 2–16 Shuaibu et al. [48] 5 AH NR NR NR MRI NR 0–82 Surov et al. [49] 6 AH NR NR NR Flexible fibreoptic endoscopy Nasal irrigations with isotonic solution and antihistamine medications 2–14 Cassano et al. [50] 7 AH Nasal allergy, S. pneumoniae NR Mouth breathing, bilateral nasal obstruction, snoring, headache, nasal allergy, earache, hearing loss Flexible fibreoptic endoscopy, radiology NR 3–14 Maheswaran et al. [51] 8 AH NR NR Snoring, mouth breathing and sleep discomfort Lateral neck radiography, nasal endoscopy Montelukast chewable tablets 4–12 Shokouhi et al. [52] Tonsils and Adenoids 4 No. Condition (NPC/ Adenoid) Causative agent(s) identified Histotype present Observed symptoms Technique used Treatment option Age range (years) References 9 AH NR NR NR Powered-shaver adenoidectomy NR 10–14 Havas and Lowinger [43] 10 AH NR NR Snoring, mouth breathing and sleep apnoea, otitis media, recurrent pharyngitis Lateral nasopharyngeal X-ray NR 0–15 Dixit and Tripathi [53] 11 AH NR NR NR Flexible fibreoptic nasopharynx endoscopy (FNE) Adenoidectomy (Backmann adenotome) 3–9 Zwierz et al. [54] 12 AH NR NR Snoring, sleep apnoea, mouth breathing, and otitis media Lateral neck radiography, fibreoptic rhinoscopy NR NR Mlynarek et al. [55] 13 AH NR NR Snoring, mouth breathing, daytime noisy breathing, sleep apnoea Flexible fibreoptic endoscopy NR 2–12 Kindermann et al. [56] 14 AH EBV NR NR EBV DNA by realtime quantitative PCR NR 2–14 Zhang et al. [57] 15 AH Adenovirus NR Rhinorrhoea, otitis media Physical examination, direct nasal endoscopy, MRI, PET Radiotherapy 10 Nicodemo et al. [19] The Link between Adenoids and Nasopharyngeal Carcinoma DOI: http://dx.doi.org/10.5772/intechopen.1001347 5 No. Condition (NPC/ Adenoid) Causative agent(s) identified Histotype present Observed symptoms Technique used Treatment option Age range (years) References 16 NPC NR Squamous cell carcinoma, nonHodgkins lymphoma, plasmacytoma, rhabdomyosarcoma NR NR Chemotherapy, radiotherapy 14–60 Iseh et al. [33] 17 NPC EBV Lympho-epithelioma NR Immunological assessment for EBV, radiology, biopsies Radio-chemotherapy 9–80 Bofares [58] 18 NPC NR Non-keratinized undifferentiated SCC NR 18 F-FDG PET/MRI NR NR Feng et al. [59] 19 NPC NR Differentiated SCC, undifferentiated SCC NR Computed tomography (CT) NR 40–75 Raica et al. [60] 20 NPC EBV NR NR Endoscopy and MRI NR 30–70 Liu et al. [61] 21 NPC NR NR NR Endoscopy and MRI NR 17–86 Shayah et al. [62] 22 NPC EBV NR NR Serum analysis for EBV antibodies NR 30–59 Ji et al. [63] 23 NPC NR NPC type I, II and III Otitis media, hearing loss, obstruction, epistaxis, headache, neuropathy, neck mass Endoscopy and MRI NR NR Wang et al. [64] 24 NPC EBV Diffused symmetrical and asymmetrical hyperplasia, mucosal lesion NR Endoscopy and MRI NR 40–62 King et al. [65] Tonsils and Adenoids 6 No. Condition (NPC/ Adenoid) Causative agent(s) identified Histotype present Observed symptoms Technique used Treatment option Age range (years) References 25 NPC NR NR NR Endoscopy, endoscopic biopsy and MRI NR 17–85 King et al. [66] 26 NPC NR Lymphoid hyperplasia NR Biopsy, MRI NR 21–94 King et al. [67] 27 NPC NR NR Nasal obstruction, epistaxis and hearing loss Endoscopic biopsy, sonography and MRI NR 21–68 Gao et al. [68] 28 NPC EBV NR NR Serum EBV capsid antigen IgA NR NR Chen et al. [69] 29 NPC NR Non-keratinized undifferentiated SCC NR PET/MRI and PET/ CT NR 24–77 Cheng et al. [70] 30 NPC NR NR NR Whole-body F-FDG PET/MRI, 18 F-FDG-PET/CT Radiation therapy, chemoradiotherapy, platinum-based chemotherapy NR Chan et al. [71] 18 31 NPC NR Non-keratinized carcinoma NR Serological testing for VCA/IgA, EA/IgA, Rta/IgG and EBNA1/IgA antibodies for EBV NR 30–70 Cai et al. [72] 32 NPC NR Undifferentiated NPC Nasal obstruction and bleeding FNE, lateral radiography, MRI, FDG-PET Radiotherapy and chemotherapy 7 Cengiz et al. [73] Table 1. List of NPC and adenoid hypertrophy cases. The Link between Adenoids and Nasopharyngeal Carcinoma DOI: http://dx.doi.org/10.5772/intechopen.1001347 7 No. Tonsils and Adenoids Similarly, unlike other cancer types that are primarily associated with the aged, NPC can also be seen in children [5, 46] and young patients [6], depicting that AH and NPC can affect both children and adults (Table 1). For instance, in South China (where NPC is an epidemic disease), hypertrophic adenoids and NPC are commonly diagnosed together, mainly in young individuals [7]. Overall, since both lesions arise in the nasopharynx, the co-occurrence of the two in a patient will be very crucial during diagnosis and treatment regimes. Thus, effective diagnosis of these lesions in cases where they coexist is very important. 5. Aetiological agents for AH and NPC Myriad causative agents have been identified to contribute to the development of AH and NPC, ranging from infectious to non-infectious agents and genetic predisposition. For AH, recurrent viral and bacterial infections in the upper respiratory tract is known to be the major cause. Reported viral pathogens include adenovirus, rhinovirus, cytomegalovirus, herpes simplex virus, EBV, coronavirus, parainfluenza virus and coxsackievirus [47, 74, 75]. France et al. [76] reported the incidence of AH in human immunodeficiency virus (HIV) patients which confirmed the findings of Olsen et al. [77]. Rout et al. also suggested that the immunity of HIV patients are compromised and further reported that adults receiving organ transplants might be prone to developing AH [78]. Aerobic and non-aerobic bacterial pathogens associated with AH include Streptococcus pneumoniae, Peptostreptococcus, Enterococcus species, Bacteroides, Streptococcus viridans, Streptococcus pyrogens, Prevotella species, Moraxella catarrhalis, Klebsiella, Fusobacterium, Staphylococcus epididermis, Escherichia coli and Haemophilus influenzae [74, 79]. Allergies, smoking, gastroesophageal reflux and air pollution are some of the non-infectious agents that cause AH. Other factors such as sinonasal malignancy and lymphoma are also associated with AH [74, 80]. Recently, Gao et al. discovered that extracellular signal-regulated kinase 1/2 activation by cysteinyl leukotriene receptor 1 may contribute to the development of AH [81]. Similarly, NACHT LRR and PYD domains-containing protein 3 (NLRP3)-mediated pyroptosis has been shown to be a mechanism through which IL-32 influences the progression of AH [82]. Additionally, a higher chance of developing AH has also been linked to several genetic predisposing factors [83–86]. However, in a recent study conducted in Moscow, Lomaeva et al. suggested that children aged 2–11 years with the IL-10G1082A genotype GG might be resistant to the development of AH [47]. Although the primary aetiology of NPC remains indefinite, EBV has strongly been associated with developing NPC and is mostly seen in the endemic areas, mostly associated with the type III [26, 28, 87–92]. Other infections such as human papillomavirus (HPV) has also been identified in NPC cases and found to be an aetiological agent for the development of NPC [37]. However, Bossi et al. recently reported that though HPV is highly seen in type I NPC, limited data is available on its association with NPC prognosis [93]. Among the HPV-positive/EBV-negative cases identified mostly in the non-endemic regions, worse patient outcomes have been observed than in EBV-positive cases [94]. A review by Chua et al. in 2016 indicated that persons with non-viral aetiologies of NPCs had lower survival rates and a worse phenotypic expression of the disease as compared to viral-associated causes [38]. This shows that the non-viral oncogenic variants have serious implications and yet their mechanistic mode of action remain undetermined. Reported non-viral aetiologies of NPCs include tobacco 8 The Link between Adenoids and Nasopharyngeal Carcinoma DOI: http://dx.doi.org/10.5772/intechopen.1001347 and smoking [87]. Risk of developing NPC have also been associated with alcohol intake, passive, intensity and frequency of smoking [95]. Though diet play a lesser role in the development of NPC currently [26], nitrosamines found in Chinesestyled salted fish and other preserved foods pose a high risk for the development of NPC [37]. These are associated with the non-keratinizing SCC of NPCs in the endemic regions while smoking and alcohol intake have been reported to cause type I NPCs mostly found in the non-endemic regions [37, 38]. Green-leafy vegetable diets seems to have a lower NPC risk as compared to animal based diets which has a twofold increased risk [96]. Additionally, frequent exposure to formaldehyde and wood dust are known causes of NPC [26]. However, other studies reported elsewhere found no excess risk in the development of NPC [97–100]. High risk genetic vulnerability have also been implicated in individuals with susceptibility loci on class I and II human leukocyte antigen (HLA) molecules in genome wide studies [29, 101–106]. Other reported genes of influence include cell cycle genes MDM2 and TP53, cell movement/adhesion gene MMP2 and DNA repair gene RAD51L1 [107]. Among the reported causative agents for AH and NPC, EBV and other lifestyle activities such as smoking and air pollution are common among the two, indicating the potential effect these agents have on adenoids and the nasopharynx. 6. Techniques for diagnosis 6.1 Adenoid hypertrophy A major issue affecting the paediatric population is diseases of ENT of which AH is no exception. Early diagnosis is therefore necessary to control symptoms and enhance treatment modalities. Zwierz et al. grouped the various diagnostic methods into two categories: namely, invasive and imaging [54]. They further grouped techniques such as rigid or flexible fibreoptic nasopharynx endoscopy (FFNE), video fluoroscopy, acoustic rhinomanometry, physical examination by the finger or a mirror through the mouth as invasive. Lateral nasopharyngeal X-ray, ultrasonography, and magnetic resonance imaging (MRI) of the nasopharynx are grouped as imaging techniques. Other imaging techniques such as computed tomography (CT) and cone beam tomography have also been reported [108]. These procedures come with high costs, the need for ENT specialists and cutting-edge expensive equipments. Though Zwierz et al. [54] reported that FFNE is invasive, Baldassari and Choi [109] highlighted that FFNE is minimally invasive and reliable among the paediatric population due to its effective and dynamic approach. Several other studies have also reported that FFNE is the gold standard for examining the nasopharynx which is less expensive as compared to the image techniques [50, 110–116]. FFNE is also the preferred choice of diagnostic procedure because it does not expose patients to unnecessary radiation as the imaging techniques do. In a recent retrospective study by Narang et al., 86% of children aged 3–10 years responded to the technique with no signs of discomfort, and symptoms of AH such as snoring, mouth-breathing and apnoeic episodes positively correlated with adenoid size [117]. Diagnosis of adenoid size in children with AH using video fluoroscopy yielded a 100% sensitivity and 90% specificity as compared to lateral skull films which showed 70% sensitivity and 55% specificity. This study concluded that video fluoroscopy is also a less invasive and reliable technique for the diagnosis of AH in the paediatric population [115]. On a lateral cephalogram ENT surgeons use methods such as that 9 Tonsils and Adenoids proposed by Handelman and Osborne which uses a trapezoid analysis to evaluate the adenoid-airway area [118]. Other methods have been formulated in recent years [119–121]. Among these, Choudhari and Shrivastav in a recent study, found the methods proposed by Holmberg and Linder-Aronson and Maw et al. to have better diagnostic accuracy due to their high sensitivity and specificity [108]. Adenoidnasopharyngeal (A/N) ratio has also been used to assess adenoid size in several AH studies [23, 53, 122–125], proposed earlier by Fujioka et al. [126]. These studies used lateral X-rays/cephalograms and found a positive correlation between adenoid size and severity of AH symptoms. Consequently, they concluded that lateral X-rays can also be used in the diagnosis of adenoid hypertrophies. Contrastingly, Mlynarek et al. concluded in their study that video rhinoscopy better correlated with adenoid size than lateral neck radioscopy [55]. However, Moideen et al. suggested that when images are not clear, FFNE should be used to give a definite diagnostic evaluation of hypertrophied adenoids [23]. In a systematic review by Major et al. which focused on comparing nasoendoscopy with other various diagnostic procedures for evaluating AH by dentists, lateral cephalogram was found to be a better option when used in combination with in-depth patient medical history [127]. Intra-operative mirror exam have also been used to assess adenoid size using the A/N ratio in comparison with FFNE findings [125, 128]. 6.2 Nasopharyngeal cancer Tissue biopsy is the gold standard for definite diagnosis of NPC though it is invasive [66]. Since EBV is highly associated with the occurrence of NPC [129], circulating free plasma EBV DNA has been used as a non-invasive biomarker to screen the disease, suggest treatment options and monitor the disease prognosis and recurrence [130, 131]. This technique produced an outstanding specificity (97.1%) and sensitivity (98.6%) in a prospective study where screening was done in a large sample of Chinese asymptomatic males aged between 40 and 69 years. The study concluded that this technique is reliable in detecting early stages of NPC which is advantageous in monitoring effective treatment and preventing worse disease outcomes [130]. In a more recent meta-analysis, EBV DNA gave a higher diagnostic accuracy than its related antibodies (VC-IgA, EBNA1-IgA and Rta-IgG) [132]. Early stages of NPC which sometimes presents with asymptomatic patients can be detected with immunoglobulin A (IgA) antibodies against EBV using various enzyme-linked immunosorbent assay (ELISA) and chemiluminescent immunoassays kits [63, 69, 133, 134]. Similarly, a meta-analysis of 21 studies by Li et al. also showed that the presence of VC/IgA in NPC-positive serum is suggestive of the presence of the disease [135]. However, a combined detection of EBV capsid antigen-IgA (VC-IgA) and early lytic gene (BRLF1) transcription activator (Rta)-IgG have been reported to give better serodiagnosis of NPC than VC/IgA alone in a Southern Chinee population [72]. In 130 EBV-positive individuals who were NPC asymptomatic, 7 cases of NPC were identified when fibreoptic endoscopy was combined with biopsy in the evaluation of some sites of the nasopharynx [136]. A combined imaging technique using positron emission tomography (PET) and MRI (PET/MRI) have shown better diagnostic images than PET/CT technique [70]. A similar observation was reported [71] where images from PET/MRI were more detailed and succinct than those of PET/CT. PET/MRI therefore produced definite images that enhanced staging procedures in NPC. In a radiomic study, Feng et al. also 10 The Link between Adenoids and Nasopharyngeal Carcinoma DOI: http://dx.doi.org/10.5772/intechopen.1001347 developed a combined radiomic model based on fluorine-18 fludeoxyglucose (fFE)PET/MRI and PET semiquantitative parameters (metabolic tumour volume, total lesion glycolysis and standardized uptake value). They concluded that this model was also reliable in the staging of NPC [59]. The use of MRI in the early stages of NPC is however not highly recommended because of its diminished sensitivity in detecting small mucosal lesions. Contrastingly, because of its remarkable sensitivity, nasopharynx MRI with gadolinium enhancement is encouraged for use in localized staging of NPC [137]. In a population study, Liu et al. compared MRI with conventional endoscopy in the detection of NPC and concluded that MRI has a better sensitivity than endoscopy [61]. Raica et al. reported that neither clinical or endoscopic examination is a clear-cut technique in detecting the extent of tumour metastasis observed in NPC. This may be because the tumours are tiny during the initial endoscopic examination [137], located in the submucosal layer [136], or present in conjunction with hyperplasia [138]. Additionally, the lateral pharyngeal recess may be structurally difficult to find due to its location which hinders a clinician’s ability to identify an occult NPC [64, 139]. Raica et al. however stated in their study of 16 patients with different histologic forms of SCC which implored the use of CT and concluded that CT scan is able to predict the staging of NPC [60]. Sonography has been compared with MRI in the diagnosis of NPC among endemic population. Similar detection of cancer was observed between the two techniques in terms of sensitivity, specificity and accuracy [68]. In a parallel study where the sensitivity and specificity of ultrasonography was compared with endoscopy, similar observations were recorded in the detection of NPC [140]. In cases of NPC where AH is concurrently diagnosed, MRI is the best option to distinguish the two lesions [141, 142]. In a case report of a 7-year-old boy who presented with nasal congestion and obstruction, AH was suspected. However, further diagnosis using immunohistochemistry revealed that the histology of the tissue mass was undifferentiated NPC [73]. Thus, tissue specific antibodies can be used alongside to aid validate the initial diagnosis to prevent false results. A summary of the techniques used in the diagnosis of AH and NPC is presented in Table 1. Although similar diagnostic techniques have been reported for NPC and AH with promising results, it is recommended that well defined standards be established to help in the prompt diagnosis of the lesions in both endemic and non-endemic regions. This will enhance effective differential diagnosis, better prognostic measures, treatment modalities and increase survival rates among patients. 7. Treatment and future perspectives NPC have mostly been treated using platinum based chemotherapy, radiotherapy or chemoradiotherapy [33, 71]. In the more advanced stages such as stage IVB, other options include the use of immunotherapy alone or in combination with chemotherapy [143]. Also, chemotherapy plus targeted therapy (Cetuximab) or immunotherapy may be other options used in this more advanced stage [144]. In recurrent NPC, endoscopic surgery is also done to reduce tumour load before radiotherapy. Other options include chemotherapy or immunotherapy (or both). The targeted drug cetuximab may be given along with chemotherapy. Hence, immunotherapy and targeted therapy might be the last treatment option for advanced stage or recurrent NPC. The two treatment regimens (targeted therapy and immunotherapy) have shown preliminary antitumour effects, and have acceptable adverse effects [143]. 11 Tonsils and Adenoids For adenoids, they are treated primarily by adenoidectomy [48, 54]. Other treatment modalities for adenoids include nasal irrigations with an isotonic solution and antihistamine medications [50] and chewing Montelukast tablets [52]. However, there are unique cases where there is co-existence of benign or hypertrophic adenoids with NPC. In such instances, these non-malignant tissues should technically not be considered as gross tumour volume (GTV) during radiotherapy. This is because, distinction of adjacent non-malignant adenoidal tissues will allow for precise measurement of GTV to avoid overdosed radiation and guide delivery of radiation to reduce non-specific toxicity in normal tissue. Furthermore, the adenoids and NPC may have different responses to chemoradiotherapy and radiotherapy [11, 142]. Lastly, the advent of liquid biopsy analysis such as circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), extracellular vesicles and micro-RNAs (miRNAs) in recent years, have demonstrated the feasibility of applying these biomarkers as a prognostic and/or predictive tool in patients with NPC [145]. These methods not only determine the heterogeneity of the tumour, but can also detect mutations or markers that are potentially druggable, hence enhancing the delivery of targeted therapy for effective treatment of the disease [144, 146]. 8. Conclusion From this review, enough evidence points to the fact that both AH and NPC have a common link based on the anatomical location and pathologies. More specifically, similar symptoms and common aetiological agents are observed in both disease conditions, and prevalent in both children and adults. Author details Du-Bois Asante1,2*, Patrick Kafui Akakpo3 and Gideon Akuamoah Wiafe2 1 Department of Forensic Science, University of Cape Coast, Ghana 2 Department of Biomedical Sciences, University of Cape Coast, Ghana 3 Department of Pathology, University of Cape Coast, Ghana *Address all correspondence to: [email protected] © 2023 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, provided the original work is properly cited. 12 The Link between Adenoids and Nasopharyngeal Carcinoma DOI: http://dx.doi.org/10.5772/intechopen.1001347 References [1] Hellings P, Jorissen M, Ceuppens JL. The Waldeyer’s ring. Acta Oto-RhinoLaryngologica Belgica. 2000;54:237-241 [2] Schupper AJ, Nation J, Pransky S. Adenoidectomy in children: What is the evidence and what is its role? Current Otorhinolaryngology Reports. 2018;6:6473. DOI: 10.1007/s40136-018-0190-8 [3] Barrett AW, Speight PM. Perineural invasion in adenoid cystic carcinoma of the salivary glands: A valid prognostic indicator? Oral Oncology. 2009;45:936-940. DOI: 10.1016/j. oraloncology.2009.07.001 [4] Larem A, Al Duhirat E, Omer H. Nasopharyngeal cancer. In: Al-Qahtani A, Haidar H, Larem A, editors. Textb. 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