Nasopharyngeal Carcinoma: Causes and Risk Factors

Introduction

Nasopharyngeal carcinoma (NPC) is malignant that arises from the nasopharynx epithelium. The nasopharynx is situated near the eustachian tubes at the back of the nose (see figure 1). The symptoms of NPC include an enlarged lymph node in the neck, bleeding from the mouth or nose, hearing loss, and difficulty breathing through the nose ¹. The disease is endemic to China and has shown variable occurrence rates ranging from high incidences in southeast Asia to lower rates in northern parts. In addition, the U.S. and Asian immigrants have also higher chances of getting infected with the disease compared to American-born Asians as well as Inuit in Alaska. Non-endemic regions have an incidence rate of less than 1 per 100,000 people. At the same time, per 100,000 in endemic areas, 15 to 20 females and 25 to 30 males are infected with the disease ². In the modern world, cancer has been among the leading cause of death to people. Therefore, following the dangers associated with cancer, there has been an increased concern in the research for the best therapeutic methods that can help manage NCP at an early stage.

Factors Impacting the Disease

Risk factors that increase the risk of developing NPC include sex, race, age, salt-cured foods, EBV, family history, and tobacco and alcohol. NPC occurs at any age but is most commonly diagnosed among adults aged 30 to 50 ³. When cooking salt-cured foods like preserved vegetables and fish, chemicals are released in the steam and can enter the nasal cavity, causing an increased risk of NPC. At an early age, when an individual is exposed to these chemicals, it even worsens the risks. The disease has been caused by a complex interplay of Epstein-Barr virus (EBV) infection and genetic susceptibility. EBV is the most common virus that produces mild signs and symptoms similar to a cold, and sometimes it can cause infectious mononucleosis ⁴. The virus has been associated with many rare cancers, including NPC. Many factors, including infections, environmental factors, and genetic susceptibility, impact the development of the incidence.

The pathogenesis of NPC has been associated with multiple genes, like human leukocyte antigen genes at chromosome 6 and other genes located at different chromosomes. EBV is highly related to the disease due to its potential to activate and inhibit multiple mechanisms and processes in the host cell while changing it into a cancerous cell ⁵. EBV impacts cells bringing its RNA molecules, which influence the host cells. Although some of the risk factors of the disease cannot be controlled, it has become possible to make lifestyle changes that contain it, such as stopping the use of drugs and substances.

NPC is diagnosed by biopsy of the tumor using a small endoscope, imaging techniques, and testing of the tumor for EBV. After diagnosis, the disease is treated using radiotherapy, surgical interventions, and chemotherapy. Radiation is suitable for locoregional lesions as non-keratinizing varieties are very radiosensitive. Since the disease is highly radiosensitive and chemo, in advanced locoregional disease, the mainstay of management is concomitant chemoradiotherapy ⁶. Chemotherapy is done with distant metastasis using agents like 5-fluorouracil and cisplatin. Surgical intervention is done only as a salvage option for distant oligo-metastasis, together with radio ablation and radiotherapy.

The gap in the Knowledge

Research on NPC has shown a gap in knowledge such that most patients suffering from the disease have presented when in an advanced stage, causing poor prognosis. Late presentation among patients has been associated with the delayed seeking of medical advice and confusing and misleading disease symptoms among clinicians. In addition, difficulty in medical examination of the nasopharynx and during examination spread of a silent submucosal lesion with a regular appearance has been a challenge to manage NPC ⁷. Research shows that eating a diet high in salt-cured meats and fish increases the risk of developing the disease. Therefore, to control the disease, it is important to practice eating a healthy diet rich in vegetables and fruits and avoid smoking and drinking alcohol as they contain toxic chemicals. Certain occupations also put individuals at risk of developing NPC as it exposes them to chemicals such as formaldehyde and EBV ⁸. Understanding the type of occupation can help put measures that prevent the individual from exposure to potential chemicals that can result in NPC.

Bioengineering Method

In this assignment, the two papers using bioengineering methods are articles of Yuan et al. and Qiang et al. The article of Yuan et al. involves research on EBV infection-induced GPX4-promoting chemoresistance and tumor progression in NPC. The article asserts that EBV was the first oncogenic virus recognized in people and was mainly related to myriad lymphoid and epithelial cancers, including NPC. However, existing research has not thoroughly explained ferroptosis’s interrelation and role in cancer therapy resistance. The article shows how EBV infection decreases the NPC cells’ sensitivity to ferroptosis by activating the p62-Keeo1-NRF2 signaling pathway in line with the upregulation of GPX4 and SC7A11 expression ⁹. The article’s findings also showed that reducing endogenous GPX4 using particular inhibitors potentially advanced the chemosensitivity of EBV-infected NPC cells. It was depicted that the knockdown of GPX4 suppresses the spread and colony development of NPC, including other cancerous types. Therefore, the article concluded that EBV infection had essential effects on redox homeostasis, which revealed a difficult role for GPX4 in tumor progression.

The article provides a possible new target for EBV-related tumors. Yuan et al. reveal that EBV infection declined ferroptosis in NPC cells and ferroptosis induced by GPX4 inhibition interrelated with EBV lytic reactivation. In addition, the research showed to have activated the p62-Keap1-NRF2 and upregulated GPX4 expression in NPC cells. GPX4 was interrelated with chemoresistance in EBV-infected NPC cells and extreme hospice findings in cancer patients ¹⁰. The formation of colony and proliferation of GPX4 in NPC cells was significantly reduced through the absence of ferroptosis inducers, and it also interacted with the TAK1-TAB complex. Ferroptosis plays a significant role in suppressing tumors, giving new opportunities for cancer therapy. The oncogenic function of GPX4 in cancer gives it probability as a therapeutic target for NPC treatment.

The article of Qiang et al. provides in-depth research on the prognostic, predictive system that depends on deep learning for locoregionally advanced (LA) NPC. The paper demonstrates how images from magnetic resonance imaging (MRI) are essential data for predictive assessment in NPC. In the article, the author created a prognostic system depending on the MRI features and medical data of LA-NPC patients to distinguish low-risk patients with whom simultaneous chemoradiotherapy is appropriate. The article establishes findings as to whether patients with stage III and IVA require aggressive treatment plans, including induction chemotherapy with chemoradiotherapy ¹¹. The prognostic staging system utilized MRI features for predictive models. In contrast, others employed clinical indicators, including EBV DNA, body mass index, and age, due to their closeness to the prognosis of NPC patients. According to Qiang et al. (2), deep learning methods like convolutional neural networks (CNN) have become common in analyzing nonstructural MRI data showing powerful image feature-capturing capabilities.

The article of Qiang et al. aims at extracting MRI features using a 3-D CNN model, integrating image features and clinical structural factors using an extreme gradient boosting (XGBoost) model for assigning overall scores for every patient and classifying LA-NPC patients of low-risks and high-risks depending on the threshold value of scores ¹². The use of a prognostic, predictive system incorporated with 3D-CNN and XGBoost algorithms was projected to reveal extreme variability in tumor traits on MRI. the research was perceived necessary as the model showed improvement of the survival predictions and subsequently helping healthcare givers in making treatment decisions for LA-NPC patients.

Conclusion

NPC is a disease that affects mainly people in China and Southeast Asia, with men being more prone to the infection than women. The disease is caused by many risk factors, including sex, race, age, salt-cured foods, EBV, family history, and tobacco and alcohol. In the current research, a knowledge gap has been revealed by a late presentation of the disease among patients due to a lack of education, delayed medication, and misleading disease symptoms for clinicians. In addition, difficulty in the medical examination of the nasopharynx has been a challenge to manage NPC. However, bioengineering tools have been used to help manage the disease, and people are encouraged to avoid any potential risk that can cause infection.

Works Cited

Chua, Melvin LK, et al. “Nasopharyngeal carcinoma.” The Lancet 387.10022 (2016): 1012–1024. Web.

Qiang, Mengyun, et al. “A prognostic, predictive system based on deep learning for locoregionally advanced nasopharyngeal carcinoma.” JNCI: Journal of the National Cancer Institute 113.5 (2021): 606–615.

Wei, William I., and Jonathan ST Sham. “Nasopharyngeal carcinoma.” The Lancet 365.9476 2005: 2041-2054. Web.

Yuan, Li et al. “EBV infection-induced GPX4 promotes chemoresistance and tumor progression in nasopharyngeal carcinoma.” Cell Death & Differentiation (2022): 1-15.

Footnotes

1. Wei, William I., and Jonathan ST Sham. “Nasopharyngeal carcinoma.” The Lancet 365.9476 2005: 2041-2054. Web.
2. Chua, Melvin LK, et al. “Nasopharyngeal carcinoma.” The Lancet 387.10022 (2016): 1012–1024. Web.
3. Chua, Melvin LK, et al. “Nasopharyngeal carcinoma.” The Lancet 387.10022 (2016): 1012–1024. Web.
4. Wei, William I., and Jonathan ST Sham. “Nasopharyngeal carcinoma.” The Lancet 365.9476 2005: 2041-2054. Web.
5. Wei, William I., and Jonathan ST Sham. “Nasopharyngeal carcinoma.” The Lancet 365.9476 2005: 2041-2054. Web.
6. Chua, Melvin LK, et al. “Nasopharyngeal carcinoma.” The Lancet 387.10022 (2016): 1012–1024. Web.
7. Chua, Melvin LK, et al. “Nasopharyngeal carcinoma.” The Lancet 387.10022 (2016): 1012–1024. Web.
8. Wei, William I., and Jonathan ST Sham. “Nasopharyngeal carcinoma.” The Lancet 365.9476 2005: 2041-2054. Web.
9. Yuan, Li et al. “EBV infection-induced GPX4 promotes chemoresistance and tumor progression in nasopharyngeal carcinoma.” Cell Death & Differentiation (2022): 1-15.
10. Yuan, Li et al. “EBV infection-induced GPX4 promotes chemoresistance and tumor progression in nasopharyngeal carcinoma.” Cell Death & Differentiation (2022): 1-15.
11. Qiang, Mengyun, et al. “A prognostic, predictive system based on deep learning for locoregionally advanced nasopharyngeal carcinoma.” JNCI: Journal of the National Cancer Institute 113.5 (2021): 606–615.
12. Qiang, Mengyun, et al. “A prognostic, predictive system based on deep learning for locoregionally advanced nasopharyngeal carcinoma.” JNCI: Journal of the National Cancer Institute 113.5 (2021): 606–615.