-
Chinese Journal of Cancer Nov 2014Epstein-Barr virus (EBV) infection is closely associated with undifferentiated nasopharyngeal carcinoma (NPC), strongly implicating a role for EBV in NPC pathogenesis;... (Review)
Review
Epstein-Barr virus (EBV) infection is closely associated with undifferentiated nasopharyngeal carcinoma (NPC), strongly implicating a role for EBV in NPC pathogenesis; conversely, EBV infection is rarely detected in normal nasopharyngeal epithelial tissues. In general, EBV does not show a strong tropism for infecting human epithelial cells, and EBV infection in oropharyngeal epithelial cells is believed to be lytic in nature. To establish life-long infection in humans, EBV has evolved efficient strategies to infect B cells and hijack their cellular machinery for latent infection. Lytic EBV infection in oropharyngeal epithelial cells, though an infrequent event, is believed to be a major source of infectious EBV particles for salivary transmission. The biological events associated with nasopharyngeal epithelial cells are only beginning to be understood with the advancement of EBV infection methods and the availability of nasopharyngeal epithelial cell models for EBV infection studies. EBV infection in human epithelial cells is a highly inefficient process compared to that in B cells, which express the complement receptor type 2 (CR2) to mediate EBV infection. Although receptor(s) on the epithelial cell surface for EBV infection remain(s) to be identified, EBV infection in epithelial cells could be achieved via the interaction of glycoproteins on the viral envelope with surface integrins on epithelial cells, which might trigger membrane fusion to internalize EBV in cells. Normal nasopharyngeal epithelial cells are not permissive for latent EBV infection, and EBV infection in normal nasopharyngeal epithelial cells usually results in growth arrest. However, genetic alterations in premalignant nasopharyngeal epithelial cells, including p16 deletion and cyclin D1 overexpression, could override the growth inhibitory effect of EBV infection to support stable and latent EBV infection in nasopharyngeal epithelial cells. The EBV episome in NPC is clonal in nature, suggesting that NPC develops from a single EBV-infected nasopharyngeal epithelial cell, and the establishment of persistent and latent EBV infection in premalignant nasopharyngeal epithelium may represent an early and critical event for NPC development.
Topics: Carcinoma; Cell Transformation, Neoplastic; Cells, Cultured; Epithelial Cells; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nasopharynx; Precancerous Conditions
PubMed: 25223910
DOI: 10.5732/cjc.014.10169 -
International Journal of Medical... 2021To analyze the prevalence proportions and prognostic factors of synchronous distant metastases in patients with tonsil squamous cell carcinomas (TSCC).
BACKGROUND
To analyze the prevalence proportions and prognostic factors of synchronous distant metastases in patients with tonsil squamous cell carcinomas (TSCC).
METHODS
TSCC patients were extracted from the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2014. We examined the association between clinical manifestations and distant metastases using Chi-squared tests. Predictors of 5-year survival were assessed using univariate and multivariate analyses.
RESULTS
A total of 6193 patients were analyzed and lung was the most common site of distant metastases. Poorly/undifferentiated differentiation was found to be significantly correlated with lung metastasis (p=0.033) and liver and bone metastases were associated with African American (p=0.000 and p=0.000, respectively). A higher T classification was associated with higher prevalence of lung, liver, bone and brain metastasis (p=0.000, p=0.000, p=0.000 and p=0.007, respectively). The same results were found in N classification in lung, liver, and bone metastasis (p=0.000, p=0.000, and p=0.000, respectively). Worse prognosis was associated with older age, Blacks, lower grade, higher T and N classification, no surgery therapy and more metastatic sites.
CONCLUSION
Lung was the most frequent lesion of synchronous distant metastases and liver and bone metastases were associated with African American. Higher T and N classification were independent prognostic parameters for higher prevalence of lung, bone, liver and brain metastasis. Worse prognosis was associated with older age, African Americans, lower grade, higher T and N classification, no surgery therapy and more metastatic sites.
Topics: Adolescent; Adult; Black or African American; Age Factors; Aged; Aged, 80 and over; Asian; Bone Neoplasms; Brain Neoplasms; Female; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Palatine Tonsil; Prevalence; Prognosis; Risk Factors; SEER Program; Squamous Cell Carcinoma of Head and Neck; Tonsillar Neoplasms; United States; White People; Young Adult
PubMed: 33390822
DOI: 10.7150/ijms.50966 -
PloS One 2023Squamous papillomas (SPs) of the head and neck are usually benign lesions associated with human papilloma virus (HPV) infection. However, the reported HPV detection...
Squamous papillomas (SPs) of the head and neck are usually benign lesions associated with human papilloma virus (HPV) infection. However, the reported HPV detection rates vary widely, especially with respect to anatomical distribution. The etiology of SPs in the head and neck remains unclear; analyzing HPV genotypes of SPs based on anatomical sites could assist in clarifying the pathogenesis of SPs in the head and neck. Therefore, the aim of this study was to review the prevalence, subtypes, and anatomical distribution of HPV in head and neck SPs at a hospital in China; we also investigated whether p16, a marker of HPV infection in oropharyngeal carcinoma, could serve as a surrogate marker for HPV in head and neck SPs. The presence of HPV DNA of 23 types (5 low-risk HPV and 18 high-risk HPV types) was detected via real-time PCR. p16 immunohistochemistry was performed using SP sections. Age, sex, anatomical location, and HPV subtype were recorded for each case. In total, 105 SPs were identified, including 47 in the larynx, 42 in the pharynx, 6 in the external auditory canal (EAC), 5 in the oral cavity, and 5 in the nasal cavity. HPV was found in 57 (54.3%) cases, with the highest positivity rate in the larynx (46/47; 97.9%). Only 5/42 (11.9%) patients showed HPV positivity in the pharynx. HPV incidence was highly dependent on the anatomical site. SPs in the larynx and EAC were more likely to carry HPV than those in other anatomical sites. High-risk HPV infections were rarely associated with SPs in the head and neck region. The sensitivity and specificity of p16 immunohistochemistry for HPV infection were 88% and 96%, respectively. There may be an association between p16 and HPV infection in head and neck SPs, but further studies are needed to validate this assertion.
Topics: Humans; Head and Neck Neoplasms; Papillomavirus Infections; Papilloma; Mouth; Carcinoma, Squamous Cell; Genotype; Cyclin-Dependent Kinase Inhibitor p16; Papillomaviridae; DNA, Viral
PubMed: 37566623
DOI: 10.1371/journal.pone.0290004 -
Ear, Nose, & Throat Journal 2019Necrotizing sialometaplasia (NSM) is a benign, reactive metaplastic condition of the minor salivary gland tissue typically seen in the setting of injury, chemical or...
Necrotizing sialometaplasia (NSM) is a benign, reactive metaplastic condition of the minor salivary gland tissue typically seen in the setting of injury, chemical or traumatic, and is nonneoplastic and self-limited. The diagnosis may be challenging as it may clinically mimic malignancy. We present the case of a 74-year-old male with a 1 pack per day smoking history for 60 years who presented with a reported 20-pound weight loss, dysphagia, and dysphonia progressing over the course of 6 months and found to have a 3.5-cm hypopharyngeal mass on computed tomography imaging and fiberoptic laryngoscopy. Initial frozen section of the mass was concerning for squamous cell carcinoma in situ, but permanent specimens returned as nondiagnostic. Repeat biopsy established a diagnosis of NSM. Two-month follow-up showed complete resolution of the mass. Clinicians should be aware that NSM may present in unusual locations when considering differential diagnoses for laryngeal masses and evaluating for malignancy.
Topics: Aged; Humans; Hypopharynx; Male; Pharyngeal Diseases; Sialometaplasia, Necrotizing
PubMed: 30966809
DOI: 10.1177/0145561319840826 -
Acta Medica Okayama Dec 2021The long-term changes in tissues implanted in the oral cavity and pharynx after head and neck reconstruction have not been fully evaluated. This study aimed to clarify...
Morphological Changes and Durability of Skin and Mucosal Flaps in Intraoral and Pharyngeal Reconstructions: Long-term Follow-up and Literature Review for Potential Second Carcinomas.
The long-term changes in tissues implanted in the oral cavity and pharynx after head and neck reconstruction have not been fully evaluated. This study aimed to clarify the morphological changes, long-term durability, and potential for secondary carcinogenesis in such tissues. In our single-center study, the rough morphological changes in 54 cases of intraoral and pharyngeal skin and mucosal flaps were evaluated more than 10 years after flap transfer. In addition, the literature on the development of second carcinomas from skin flaps was reviewed. The mean follow-up period for transferred flaps was 148 months. The reconstruction areas and the probability of morphological changes were significantly correlated (p=0.006), especially in cases with tongue, lower gingiva, and buccal mucosal reconstruction. Free jejunal flap surfaces were well maintained, whereas tubed skin flaps showed severe morphological changes in cases with pharyngeal reconstruction. None of the flaps in our series developed second primary carcinomas. Skin flaps generally had good durability for > 10 years in intraoral environments, while mucosal flaps had better durability for pharyngeal reconstruction. Second squamous carcinomas arising from skin flaps are extremely rare; however, surgeons should take this possibility into consideration and conduct meticulous and long-term follow-up.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Follow-Up Studies; Free Tissue Flaps; Humans; Male; Middle Aged; Neoplasms, Second Primary; Pharynx; Plastic Surgery Procedures; Retrospective Studies; Young Adult
PubMed: 34955541
DOI: 10.18926/AMO/62813 -
Chinese Journal of Cancer Nov 2014Although the Epstein-Barr virus (EBV) has spread to all populations in the world, EBV-associated nasopharyngeal carcinoma (NPC) is prevalent only in South China and... (Review)
Review
Although the Epstein-Barr virus (EBV) has spread to all populations in the world, EBV-associated nasopharyngeal carcinoma (NPC) is prevalent only in South China and Southeast Asia. The role of EBV in the malignant transformation of nasopharyngeal epithelium is the main focus of current researches. Radiotherapy and chemoradiotherapy have been successful in treating early stage NPC, but the recurrence rates remain high. Unfortunately, local relapse and metastasis are commonly unresponsive to conventional treatments. These recurrent and metastatic lesions are believed to arise from residual or surviving cells that have the properties of cancer stem cells. These cancer stem-like cells (CSCs) have the ability to self-renew, differentiate, and sustain propagation. They are also chemo-resistant and can form spheres in anchorage-independent environments. This review summarizes recent researches on the CSCs in EBV-associated NPC, including the findings regarding cell surface markers, stem cell-related transcription factors, and various signaling pathways. In particular, the review focuses on the roles of EBV latent genes [latent membrane protein 1 (LMP1) and latent membrane protein 2A (LMP2A)], cellular microRNAs, and adenosine triphosphate (ATP)-binding cassette chemodrug transporters in contributing to the properties of CSCs, including the epithelial-mesenchymal transition, stem-like transition, and chemo-resistance. Novel therapeutics that enhance the efficacy of radiotherapy and chemoradiotherapy and inhibitors that suppress the properties of CSCs are also discussed.
Topics: Carcinoma; Cell Transformation, Neoplastic; China; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Herpesvirus 4, Human; Humans; MicroRNAs; Multidrug Resistance-Associated Proteins; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nasopharynx; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplastic Stem Cells; Signal Transduction; Viral Matrix Proteins
PubMed: 25223912
DOI: 10.5732/cjc.014.10081 -
Cancer Cytopathology Feb 2019
Topics: Carcinoma, Neuroendocrine; Carcinoma, Small Cell; Head and Neck Neoplasms; Humans; Lung Neoplasms; Oropharynx; Papillomavirus Infections
PubMed: 30661306
DOI: 10.1002/cncy.22094 -
International Journal of Molecular... Aug 2022Head and neck squamous cell carcinomas (HNSCCs) are a type of cancer originating in the mucosal epithelium of the mouth, pharynx, and larynx, the sixth most common...
Head and neck squamous cell carcinomas (HNSCCs) are a type of cancer originating in the mucosal epithelium of the mouth, pharynx, and larynx, the sixth most common cancer in the world. However, there is no effective treatment for HNSCCs. More than 90% of HNSCCs overexpress epidermal growth factor receptors (EGFRs). Although small molecule inhibitors and monoclonal antibodies have been developed to target EGFRs, few EGFR-targeted therapeutics are approved for clinical use. Ferroptosis is a new kind of programmed death induced by the iron catalyzed excessive peroxidation of polyunsaturated fatty acids. A growing body of evidence suggests that ferroptosis plays a pivotal role in inhibiting the tumor process. However, whether and how ferroptosis-inducers (FINs) play roles in hindering HNSCCs are unclear. In this study, we analyzed the sensitivity of different HNSCCs to ferroptosis-inducers. We found that only tongue squamous cell carcinoma cells and laryngeal squamous cell carcinoma cells, but not nasopharyngeal carcinoma cells, actively respond to ferroptosis-inducers. The different sensitivities of HNSCC cells to ferroptosis induction may be attributed to the expression of and ferritin heavy chain () since a high level of is associated with the poor prognostic survival of HNSCCs, but knocked down can promote HNSCC cell death. Excitingly, the ferroptosis-inducer RSL3 plays a synthetic role with EGFR monoclonal antibody to inhibit the survival of nasopharyngeal carcinoma cells (CNE-2), which are insensitive to both ferroptosis induction and EGFR inhibition due to a high level of and a low level of , respectively. Our findings prove that plays a vital role in ferroptosis resistance in HNSCCs and also provide clues to target HNSCCs resistant to ferroptosis induction and/or EGFR inhibition.
Topics: Antibodies, Monoclonal; Carcinoma, Squamous Cell; Cell Line, Tumor; Cetuximab; ErbB Receptors; Ferroptosis; Head and Neck Neoplasms; Humans; Squamous Cell Carcinoma of Head and Neck; Tongue Neoplasms
PubMed: 36012290
DOI: 10.3390/ijms23169014 -
Clinical Oral Investigations Mar 2022This study aims to evaluate the usefulness of liquid-based brush cytology for malignancy diagnosis and HPV detection in patients with suspected oropharyngeal and oral...
OBJECTIVES
This study aims to evaluate the usefulness of liquid-based brush cytology for malignancy diagnosis and HPV detection in patients with suspected oropharyngeal and oral carcinomas, as well as for the diagnosis of tumoral persistence after treatment.
MATERIAL AND METHODS
Seventy-five patients with suspicion of squamous cell carcinoma of the oropharynx or oral cavity were included. Two different study groups were analyzed according to the date of the sample collection: (1) during the first endoscopy exploration and (2) in the first control endoscopy after treatment for squamous cell carcinoma. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for malignancy diagnosis as well as for HPV-DNA detection on brush cytologies were assessed.
RESULTS
Before treatment, the brush cytology showed a sensitivity of 88%, specificity of 100%, and accuracy of 88%. After treatment, it showed a sensitivity of 71%, specificity of 77%, and accuracy of 75%. HPV-DNA detection in cytology samples showed a sensitivity of 85%, specificity of 100%, and accuracy of 91% before treatment and an accuracy of 100% after treatment.
CONCLUSIONS
Liquid-based brush cytology showed good accuracy for diagnosis of oropharyngeal and oral squamous cell carcinoma before treatment, but its value decreases after treatment. Nevertheless, it is useful for HPV-DNA detection, as well as to monitor the patients after treatment.
CLINICAL RELEVANCE
Brush cytology samples are reliable for the detection of HPV-DNA before and after treatment and may be a useful method to incorporate in the HPV testing guidelines.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Mouth Neoplasms; Oropharyngeal Neoplasms; Oropharynx; Papillomavirus Infections; Sensitivity and Specificity
PubMed: 34839418
DOI: 10.1007/s00784-021-04228-5 -
International Journal of Molecular... Feb 2023Head and neck squamous cell carcinoma (HNSCC) is a term collectively used to describe all cancers that develop in the oral and nasal cavities, the paranasal sinuses, the... (Review)
Review
Head and neck squamous cell carcinoma (HNSCC) is a term collectively used to describe all cancers that develop in the oral and nasal cavities, the paranasal sinuses, the salivary glands, the pharynx, and the larynx. The majority (75%) of all newly diagnosed cases are observed in patients with locally advanced and aggressive disease, associated with significant relapse rates (30%) and poor prognostic outcomes, despite advances in multimodal treatment. Consequently, there is an unmet need for the identification and application of tools that would enable diagnosis at the earliest possible stage, accurately predict prognostic outcomes, contribute to the timely detection of relapses, and aid in the decision for therapy selection. Recent evidence suggests that DNA methylation can alter the expression of genes in a way that it favors tumorigenesis and tumor progression in HNSCC, and therefore represents a potential source for biomarker identification. This study summarizes the current knowledge on how abnormally methylated DNA profiles in HNSCC patients may contribute to the pathogenesis of HNSCC and designate the methylation patterns that have the potential to constitute clinically valuable biomarkers for achieving significant advances in the management of the disease and for improving survival outcomes in these patients.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; DNA Methylation; Carcinoma, Squamous Cell; Prognosis; Biomarkers, Tumor; Neoplasm Recurrence, Local; Head and Neck Neoplasms
PubMed: 36769317
DOI: 10.3390/ijms24032996