The diversity of inhibitory receptor co-expression patterns of exhausted CD8+ T cells in oropharyngeal carcinoma.

Exhausted CD8+ T cells (Texs) are characterized by the expression of various inhibitory receptors (IRs), whereas the functional attributes of these co-expressed IRs remain limited. Here, we systematically characterized the diversity of IR co-expression patterns in Texs from both human oropharyngeal squamous cell carcinoma (OPSCC) tissues and syngeneic OPSCC model. Nearly 60% of the Texs population co-expressed two or more IRs, and the number of co-expressed IRs was positively associated with superior exhaustion and cytotoxicity phenotypes. In OPSCC patients, programmed cell death-1 (PD-1) blockade significantly enhanced PDCD1-based co-expression with other IR genes, whereas dual blockades of PD-1 and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) significantly upregulated CTLA4-based co-expression with other IR genes. Collectively, our findings demonstrate that highly diverse IR co-expression is a leading feature of Texs and represents their functional states, which might provide essential clues for the rational selection of immune checkpoint inhibitors in treating OPSCC.

Analysis of characteristics of and risk factors for otological symptoms after COVID-19 infection.

The purpose of this study was to explore the characteristics of and risk factors for otological symptoms after contracting COVID-19. We invited 468 participants who had been infected with COVID-19 to participate in a survey. 310 (66.2%) were women and 158 (33.8%) were men. The mean age is 38.73 (12.21) years. The questionnaire included their basic information, symptoms and symptom duration after SARS-CoV-2 infection, number of vaccine doses received, and details regarding otological symptoms. In total, 106/468 (22.6%) participants experienced tinnitus, 66/468 (14.1%) hearing loss, 103/468 (22.0%) aural fullness, and 71/468 (15.2%) dizziness. Women were more prone to experience tinnitus (P = 0.022) and dizziness (P = 0.001) than men. The group with hearing loss were older (P = 0.025), and their initial COVID-19 symptoms lasted longer (P = 0.028) than those of patients without. Patients with aural fullness were more likely to experience fatigue than patients without (P = 0.002). Patients experiencing dizziness were more likely to experience pharyngalgia (P = 0.040) and fatigue (P = 0.005) than those without. The number of vaccine doses was positively associated with the resolution of otological symptoms (P = 0.035). Multiple logistic regression analysis revealed that sex was an independent risk factor for tinnitus (odds ratio [OR], 1.802; 95% confidence interval [CI], 1.099-2.953; P = 0.020), the duration of initial COVID-19 symptoms for hearing loss (OR, 1.055; 95% CI, 1.008-1.105; P = 0.023), and sex for dizziness (OR, 2.870; 95% CI, 1.489-5.535; P = 0.002). Sex, age, COVID-19-related fatigue, and the duration of initial COVID-19 symptoms may affect the occurrence of otological symptoms, and vaccines may aid their resolution.

Prognostic effects of previous cancer history on patients with major salivary gland cancer.

OBJECTIVES: To explore the prognostic effects of previous cancer history on patients with major salivary gland cancer (SGC). SUBJECTS AND METHODS: SGC patients with (sec-SGC) and without (one-SGC) a previous cancer from the SEER database were identified. Cox proportional hazards regression (CoxPH) models were used to compare the prognosis between sec-SGC and one-SGC patients. Subgroup analyses for sec-SGC patients by gender, previous cancer types, previous cancer histology, and cancer diagnosis interval (CDI) were performed. Two CoxPH models were constructed to distinguish sec-SGC patients with different prognostic risks. RESULTS: 9098 SGC patients were enrolled. Overall, sec-SGC patients (adjusted HR [aHR] = 1.26, p < 0.001), especially those with a CDI ≤ 5 years (aHR = 1.47, p < 0.001), had worse overall survival (OS) than one-SGC patients. In subgroup analysis, only sec-SGC patients with a previous head and neck cancer who were female (aHR = 2.38, p = 0.005), with a CDI ≤ 5 years (aHR = 1.65, p = 0.007) or with a previous squamous cell carcinoma (aHR = 6.52, p < 0.001) had worse OS. Our models successfully differentiated all sec-SGC patients into high-, intermediate- and low-risk groups with different prognosis. CONCLUSIONS: Sec-SGC patients with different previous cancer types, gender, CDI and previous cancer histology had varied prognosis. The models we constructed could help differentiate the prognosis of sec-SGC patients with different risks.

Low Bone Mineral Density and the Risk of Benign Paroxysmal Positional Vertigo.

OBJECTIVE: This study aimed to comprehensively analyze the relationship between low bone mineral density (BMD) and the risk of benign paroxysmal positional vertigo (BPPV) based on the large prospective population-based UK Biobank (UKB) cohort. STUDY DESIGN: Prospective population-based cohort study. SETTING: The UKB. METHODS: This prospective cohort study included UKB participants recruited between 2006 and 2010 who had information on BMD and did not have BPPV before being diagnosed with low BMD. Univariable and multivariable logistic regression models were constructed to assess the association between low BMD (overall low BMD, osteopenia, and osteoporosis) and BPPV. We further conducted sex and age subgroup analysis, respectively. Finally, the effects of antiosteoporosis and female sex hormone medications on BPPV in participants with osteoporosis were evaluated. RESULTS: In total, 484,303 participants were included in the final analysis, and 985 developed BPPV after a maximum follow-up period of 15 years. Osteoporosis was associated with a higher risk of BPPV (odds ratio [OR] = 1.37, P = .0094), whereas osteopenia was not. Subgroup analyses suggested that the association between osteoporosis and BPPV was significant only in elderly females (≥60 years, OR = 1.51, P = .0007). However, no association was observed between antiosteoporosis or female sex hormone medications and BPPV in the participants with osteoporosis. CONCLUSION: Osteoporosis was associated with a higher risk of developing general BPPV, especially in females aged ≥ 60 years old, whereas osteopenia was not associated with BPPV.

Full-duplex cylindrical vector beam multiplexing communication using spin-dependent phase modulation metasurfaces.

Cylindrical vector beam (CVB) has recently gained attention as a promising carrier for signal multiplexing owing to its mode orthogonality. However, the full-duplex multiplexing communication has not been previously explored for the lack of effective technologies to parallelly couple and separate CVB modes. Herein, we present a full-duplex solution for CVB multiplexing communication that utilizes spin-dependent phase modulation metasurfaces. By independently phase-modulating the two spin eigenstates of CVBs with the metasurface via spin-dependent orbital interactions, and loading two binary Dammann vortex gratings, we enabled an independent and reciprocal wave vector manipulation of CVBs for full-duplex (de)multiplexing operation. To demonstrate this concept, we constructed a 16-channel (including 4 CVB modes and 4 wavelengths) full-duplex CVB multiplexing communication system and achieved the bidirectional transmission of 800 Gbit/s quadrature-phase shift-keying (QPSK) signals over a 5 km few-mode fiber. Our results demonstrate the successful multiplexing and demultiplexing of 2 radial CVB modes and 2 azimuthal CVB modes in full-duplex communication with the bit-error-rates approaching 1.87 × 10-5.

Low cholesterol levels are associated with increasing risk of plasma cell neoplasm: A UK biobank cohort study.

BACKGROUND: Plasma cell neoplasms are a group of hematologic neoplasms that often develop in the elderly population. The relationship between cholesterol levels and hematologic malignancy has been identified in population studies. However, it is still unclear if there is a relationship between cholesterol levels and plasma cell neoplasm in European ancestry. METHODS: Prospective cohorts included 502,507 individuals from the UK Biobank who were followed up to 2019 and assessed total cholesterol(TC) levels, low-density lipoprotein (LDL) levels, high-density lipoprotein (HDL) levels, apolipoprotein A (ApoA) and apolipoprotein B (ApoB) as risk factors for plasma cell neoplasms with Cox proportional hazard regression and restricted cubic spline model. We also used two-sample Mendelian randomization to determine if the cholesterol level has a causal effect on developing plasma cell neoplasms. RESULTS: We observed 1819 plasma cell neoplasm cases during 14.2 years of follow-up in the UK Biobank. We found higher blood serum cholesterol levels at baseline were associated with a lower risk of plasma cell neoplasm in our study. All lipid profiles we analyzed in this study were inversely associated with plasma cell neoplasm risk (all ptrend <0.005) but triglycerides did not have such association. However, there was no suggestive association of genetically predicted serum LDL, HDL, and total cholesterol levels with multiple myeloma. CONCLUSION: Low serum total cholesterol, LDL, HDL, ApoA, and ApoB levels were all associated with increasing the risk of plasma cell neoplasm.

A Population-Based Outcome-Wide Association Study of the Comorbidities and Sequelae Following COVID-19 Infection.

BACKGROUND: Immense attention has been given to the outcome of COVID-19 infection. However, comprehensive studies based on large populational cohort with long-term follow-up are still lacking. This study aimed to investigate the risk of various short-term comorbidities (within one month) and long-term sequelae (above one month) after COVID-19 infection. METHODS: In this large prospective cohort study with 14 months follow-up information based on UK biobank, we included 16,776 COVID-19-positive participants and 58,281 COVID-19-negative participants matched for comparison. The risk of each comorbidity and sequela was evaluated by multivariable logistic regression analysis and presented as hazard ratio (HR) and 95% confidence interval (95% CI). RESULTS: COVID-19-positive individuals had a higher risk of 47 types of comorbidities within one month following COVID-19 infection, especially those who were older, male, overweight/obese, ever-smoked, with more pre-existing comorbidities and hospitalized. About 70.37% of COVID-19 patients with comorbidities had more than one co-occurring comorbidities. Additionally, only 6 high-risk sequelae were observed after one month of COVID-19 infection, and the incidence was relatively low (< 1%). CONCLUSION: In addition to long-term sequelae following COVID-19 infection, plenty of comorbidities were observed, especially in patients with older age, male gender, overweight/obese, more pre-existing comorbidities and severe COVID-19, indicating that more attention should be given to these susceptible persons within this period.

mRNA-LNP vaccination-based immunotherapy augments CD8+ T cell responses against HPV-positive oropharyngeal cancer.

Although mRNA vaccines are known as potent activators of antigen-specific immune responses against infectious diseases, limited understanding of how they drive the functional commitment of CD8+ T cells in tumor microenvironment (TME) and secondary lymphoid organs hinders their broader application in cancer immunotherapy. Here, we systematically evaluated the immunological effects of a lipid nanoparticle (LNP)-encapsulated mRNA vaccine that encodes human papillomavirus E7 protein (HPV mRNA-LNP), a tumor-specific antigen of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). HPV mRNA-LNP vaccination activated overall and HPV-specific CD8+ T cells, as well as differentially drove the functional commitment of CD8+ T cells through distinct IFN-response and exhaustion trajectories in the spleen and TME, respectively. Combination therapies of HPV mRNA-LNP vaccination with immune checkpoint blockades boosted HPV-specific CD8+ T cells while maintaining their anti-tumor function, thus further promoting tumor regression. Our results showed that the HPV mRNA-LNP vaccination combined with immune checkpoint blockade is a promising approach for immunotherapy of HPV-positive OPSCC.

Associations between immune-mediated diseases (IMDs) and the risk of HPV-associated diseases: a UK Biobank cohort analysis.

OBJECTIVES: To systematically assess the associations between various immune-mediated diseases (IMDs) and human papillomavirus (HPV)-associated diseases. DESIGN: Retrospective cohort study. SETTING: UK Biobank. PARTICIPANTS: A total of 500 371 subjects aged 40-69 years were eligible for the analysis, after excluding those with prevalent HPV-associated diseases at baseline and those who had withdrawn their informed consent or lacked information on sex. EXPOSURE: Eighty IMDs (involving allergic/atopic diseases, autoimmune diseases, immunodeficiency diseases, etc) were identified in the UK Biobank. PRIMARY AND SECONDARY OUTCOME MEASURES: The main outcome was the incidence of HPV-associated diseases (including warts and malignancies of the cervix, oropharynx, anus, penis, vulva and vagina). Cox proportional hazards model was used to estimate HRs and 95% CIs with particular adjustment for sexual behaviours. We also conducted subgroup analyses based on benign and malignant status, and anatomical sites of HPV-associated diseases, respectively. RESULTS: During a median of 12.0 years of follow-up, 2244 cases out of 500 371 subjects developed HPV-associated diseases. Overall, participants with IMDs had a higher risk of HPV-associated diseases than their controls after adjustment for sexual behaviours and other potential confounders (female: HR=1.90, 95% CI=1.66 to 2.17, p<0.001; male: HR=1.66, 95% CI=1.41 to 1.97, p<0.001). Additionally, eight individual IMDs in women (eg, asthma: HR=1.76, 95% CI=1.47 to 2.11, p<0.001) and three in men (eg, chronic nephritic syndrome: HR=6.05, 95% CI=3.32 to 11.04, p<0.001) were associated with increased risk of HPV-associated diseases. Subgroup analyses revealed significant IMD differences between benign and malignant subgroups as well as between oropharyngeal and anogenital subgroups. CONCLUSION: In this large retrospective cohort study, IMDs were significantly associated with an elevated risk of HPV-associated diseases. Besides, gender-specific and region-specific associations were also observed between individual IMDs and HPV-associated diseases.

Immobilization of purified enzyme EreB in metalorganic framework (MOF) mesopores for erythromycin degradation.

Erythromycin, a commonly used macrolide antibiotic, plays a crucial role in both human medicine and animal husbandry. However, its abuse has led to residual presence in the environment, with problems such as the emergence of resistant bacteria and enrichment of resistance genes. These issues pose significant risks to human health. Thus far, there are no effective, environmentally friendly methods to manage this problem. Enzymes can specifically degrade erythromycin without causing other problems, but their unrecyclability and environmental vulnerability hinder large-scale application. Enzyme immobilization may help to solve these problems. This study used Cu-BTC, a synthetic metal-organic framework, to immobilize the erythromycin-degrading enzyme EreB. The loading temperature and enzyme quantity were optimized. The Cu-BTC and EreB@Cu-BTC were characterized by various methods to confirm the preparation of Cu-BTC and immobilization of EreB. The maximum enzyme loading capacity was 66.5 mg g-1. In terms of enzymatic properties, immobilized EreB had improved heat (25-45 °C) and alkaline (6.5-10) tolerance, along with greater affinity between the enzyme and its substrate; Km decreased from 438.49 to 372.30 mM. Recycling was also achieved; after 10 cycles, 57.12% of the enzyme activity was maintained. After composite degradation, the antibacterial activity of erythromycin-containing wastewater was examined; the results showed that the novel composite could completely inactivate erythromycin. In summary, Cu-BTC was an ideal carrier for immobilization of the enzyme EreB, and the EreB@Cu-BTC composite has good prospects for the treatment of erythromycin-containing wastewater.

Experimental study on carbon capture characteristics of marine engine exhaust gas by activated potassium carbonate absorbent.

Post-combustion carbon capture is a direct and effective way for onboard carbon capture. Therefore, it is important to develop onboard carbon capture absorbent that can both ensure a high absorption rate and reduce the energy consumption of the desorption process. In this paper, a K2CO3 solution was first established using Aspen Plus to simulate CO2 capture from the exhaust gases of a marine dual-fuel engine in diesel mode. The lean and rich CO2 loading results from the simulation were used to guide the selection and optimization of the activators used in the experiment. During the experiment, five amino acid salt activators including SarK, GlyK, ProK, LysK, and AlaK and four organic amine activators including MEA, PZ, AEEA, and TEPA were used. Experiments only considered the activation effect of CO2 loading between lean and rich conditions. The results showed that after adding a small amount of activator, the absorption rate of CO2 by the absorbent was greatly improved, and the activation effect of organic amine activators was stronger than that of amino acid salts. Among the amino acid salts, the SarK-K2CO3 composite solution showed the best performance in both absorption and desorption. Among the amino acid salts and the organic amino activators, SarK-K2CO3 showed the best performance in strengthening the CO2 desorption while PZ-K2CO3 enhanced the CO2 absorption process the most. In the study of the concentration ratio, it was found that when the mass concentration ratio was 1:1 for SarK:K2CO3 and PZ:K2CO3, the CO2 absorption and desorption processes improved well.

Environmental factors induced macrolide resistance genes in composts consisting of erythromycin fermentation residue, cattle manure, and maize straw.

With the growing concerns about antibiotic resistance, it is more and more important to prevent the environmental pollution caused by antibiotic fermentation residues. In this study, composted erythromycin fermentation residue (EFR) with the mixture of cattle manure and maize straw at ratios of 0:10 (CK), 1:10 (T1), and 3:10 (T2) explores the effects on physicochemical characteristics, mobile genetic elements (MGEs), and antibiotic resistance genes (ARGs). Results reflected that the addition of EFR reduced the carbon/nitrogen ratio of each compost and improved the piles' temperature, which promoted the composting process. However, the contents of Na+, SO42-, and erythromycin were also significantly increased. After 30 days of composting, the degradation rates of erythromycin in CK, T1, and T2 were 72.7%, 20.3%, and 37.1%, respectively. Meanwhile, the total positive rates for 26 detected ARGs in T1 and T2 were 65.4%, whereas that of CK was only 23.1%. Further analysis revealed that ARGs responsible for ribosomal protection, such as ermF, ermT, and erm(35), dominated the composts of T1 and T2, and most were correlated with IS613, electrical conductivity (EC), nitrogen, and Zn2+. Above all, adding EFR helps to improve the nutritional value of composts, but the risks in soil salinization and ARG enrichment caused by high EC and erythromycin content should be further investigated and eliminated.

Associations Between Body Composition and Sensorineural Hearing Loss Among Adults Based on the UK Biobank.

OBJECTIVE: To explore the association between body composition and sensorineural hearing loss (SNHL). STUDY DESIGN: Cross-sectional study, prospective study and Mendelian randomization (MR) analyses. SETTING: UK Biobank. METHODS: This cross-sectional study included 147,296 adult participants with complete data on body composition and the speech-reception-threshold (SRT) test. We further conducted a prospective study with 129,905 participants without SNHL at baseline and followed up to 15 years to explore the association between body composition and new-onset SNHL. Multivariable logistic regression and Cox regression models were used. Subgroup analyses stratified by age and sex were performed. We further assessed the causal association between body composition and SNHL using two-sample MR analyses. RESULTS: Our cross-sectional study revealed that fat percentage, especially leg (odds ratio [OR] 1.46, p = .029) and arm (OR 1.43, p = .004), were significant risk factors for SNHL. However, fat-free mass, especially in the arm (OR 0.27, p < .001) and leg (OR 0.58, p < .001) showed significant protective effects against SNHL, which was substantially consistent with the results of the prospective study. In addition, we found that young women with SNHL were more susceptible to body composition indicators. However, MR analyses revealed no evidence of significant causal association. CONCLUSION: Fat percentage, especially in the leg and arm, was a significant risk factor for SNHL, whereas fat-free mass, especially in the leg and arm, had significant protective effects against SNHL, however, these associations may not be causal.

Comparison of Primary B/NKT Non-Hodgkin Lymphomas in Nasopharynx, Nasal Cavity, and Paranasal Sinuses.

OBJECTIVE: We aimed to compare clinical and survival differences between B-cell (B-NHL) and NKT-cell non-Hodgkin lymphomas (NKT-NHL) located in the nasal cavity (NC), nasopharynx, and paranasal sinuses, which are always categorized as one sinonasal type. STUDY DESIGN: Patients diagnosed with primary B-NHL and NKT-NHL in the nasal cavity, nasopharynx, and paranasal sinuses from Surveillance, Epidemiology, and End Results (SEER) database were included (1975-2017). SETTING: Population-based cohort study. METHODS: We conducted univariate and multivariate Cox regressions and Kaplan-Meier analysis to examine survival outcomes of B/NKT-NHL in the nasal cavity, nasopharynx, and paranasal sinuses, respectively. RESULTS: Overall, most B-NHL cases originated from the nasopharynx, while the majority of NKT-NHL cases occurred in the nasal cavity. Notably, the cancer-special survival (CSS) outcomes improved significantly in all sinonasal B-NHL cases over time, whereas no such improvement trend was observed in each sinonasal NKT-NHL type. Additionally, increasing age was linked with an elevated risk of death in B-NHL, particularly in the nasal cavity (Hazard ratio [HR]: 3.37), rather than in NKT-NHL. Compared with B-NHL, the adverse effect of a higher stage on CSS was more evident in NKT-NHL, particularly in its nasopharynx site (HR: 5.12). Furthermore, radiotherapy was beneficial for survival in patients with sinonasal B-NHL and NKT-NHL, except in the nasopharynx NKT-NHL. However, chemotherapy has only been beneficial for CSS in patients with paranasal sinuses B-NHL (HR: 0.42) since 2010, rather than in other types of B/NKT-NHL. CONCLUSION: Although B-NHL and NKT-NHL in the nasal cavity, nasopharynx and paranasal sinuses have similar anatomical locations, their clinicodemographics and prognoses are largely different and should be treated and studied as distinct diseases.

Biodegradation efficiency and mechanism of erythromycin degradation by Paracoccus versutus W7.

Continuous and excessive usage of erythromycin results in serious environmental pollution and presents a health risk to humans. Biological treatment is considered as an efficient and economical method to remove it from the environment. In this study, a novel erythromycin-degrading bacterial strain, W7, isolated from sewage sludge was identified as Paracoccus versutus. Strain W7 degraded 58.5% of 50 mg/L erythromycin in 72 h under the optimal conditions of 35 °C, pH 7.0, and 0.1% sodium citrate with yeast powder in mineral salt medium. It completely eliminated erythromycin from erythromycin fermentation residue at concentrations of 100 and 300 mg/L within 36 and 60 h, respectively. Erythromycin esterase (EreA) was found to be involved in erythromycin metabolism in this strain and was expressed successfully. EreA could hydrolyze erythromycin, and its maximum activity occurred at pH 8.5 and 35 °C. Finally, six intermediates of erythromycin degraded by strain W7 were detected by high performance liquid chromatography mass spectrometry. Based on the novel intermediates and enzymes, we determined two possible pathways of erythromycin degradation by strain W7. This study broadened our understanding of the erythromycin catabolic processes of P. versutus and developed a feasible microbial strategy for removing erythromycin from erythromycin fermentation residue, wastewater, and other erythromycin-contaminated environments.

Proliferative exhausted CD8+ T cells exacerbate long-lasting anti-tumor effects in human papillomavirus-positive head and neck squamous cell carcinoma.

The survival prognosis of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) is largely different, and little is known about the anti-tumor mechanism of tumor-infiltrated exhausted CD8+ T cells (Tex) in HNSCC. We performed cell-level multi-omics sequencing on human HNSCC samples to decipher the multi-dimensional characteristics of Tex cells. A proliferative exhausted CD8+ T cell cluster (P-Tex) which was beneficial to survival outcomes of patients with HPV-positive HNSCC was identified. Interestingly, P-Tex cells expressed CDK4 genes as high as cancer cells, which could be simultaneously inhibited by CDK4 inhibitors and might be a potential reason for the ineffectiveness of CDK4 inhibitors in treating HPV-positive HNSCC. P-Tex cells could aggregate in the antigen-presenting cell niches and activate certain signaling pathways. Together, our findings suggest a promising role for P-Tex cells in the prognosis of patients with HPV-positive HNSCC by providing modest but persistent anti-tumor effects.

[Overview of thyroid gland involvement and its prognostic value on advanced laryngeal cancer].

Laryngeal cancer is the second most common malignancy in the head and neck region. The guidelines recommend prophylactic thyroidectomy for patients with advanced laryngeal cancer, but its prognostic value remains elusive. In this review, the incidence, risk factors, prognostic value of thyroid invasion in patients with laryngeal cancer were reviewed. The effect of prophylactic thyroidectomy on the outcome of advanced laryngeal cancer patients was also discussed.

Clinical outcomes of temporal bone squamous cell carcinoma: A single-institution experience.

OBJECTIVES: This study aimed to investigate the survival outcomes and potential prognostic factors of patients with temporal bone squamous cell carcinoma (TBSCC) treated at our institution. METHODS: We retrospectively included patients who were diagnosed with TBSCC between 2008 and 2019. The Kaplan-Meier (KM) method was used to describe overall survival (OS), and the association between baseline characteristics and prognoses was examined using Cox proportional hazards models. RESULTS: Fifty consecutive patients with TBSCC were included in this study. The results showed that patients with advanced modified Pittsburgh (MPB)- T classifications had a poorer prognosis (T3 vs. T1-2: HR: 2.81, 95% CI: 0.34-23.43; T4 vs. T1-2: HR: 7.25, 95% CI: 0.95-55.41; p = 0.041). Meanwhile, middle ear squamous cell carcinoma (MESCC) showed a significantly worse prognosis than external auditory canal squamous cell carcinoma (EACSCC, HR: 2.65, 95% CI: 1.04-6.76, p = 0.04). CONCLUSIONS: MESCC and advanced MPB-T classifications might be considered predictors of unfavorable outcomes in patients with TBSCC, indicating that special attention should be paid to the original tumor subsite and tumor extension in the management of patients with TBSCC.

The role of HPV status in patients with overlapping grey zone cancer in oral cavity and oropharynx.

PURPOSE: We aimed to explore the clinicodemographic characteristics and prognosis of grey zone squamous cell cancer (GZSCC) located in the overlapping or ambiguous area of oral cavity and oropharynx and to identify valuable factors that would improve its differential diagnosis and prognosis. METHODS: Information of GZSCC patients in the Surveillance, Epidemiology, and End Results (SEER) database were compared to patients with oral cavity (OCSCC) and oropharyngeal (OPSCC) squamous cell carcinomas with corresponding HPV status, respectively. Kaplan-Meier method with log-rank test and multivariate Cox regression analysis were applied to assess associations between clinical characteristics and overall survival (OS). A predictive model integrating age, gender, marital status, HPV status and staging variables was conducted to classify GZSCC patients into three risk groups and verified internally by tenfold cross validation. RESULTS: A total of 3318 GZSCC, 10792 OPSCC and 6656 OCSCC patients were identified. HPV-positive GZSCC patients had the best 5-year OS as HPV-positive OPSCC (81% vs. 82%). However, the 5-year OS of HPV-negative/unknown GZSCC (43%/42%) were the worst among all groups, indicating that HPV status and the overlapping nature of tumors were valuable prognostic predictors in GZSCC patients. Compared with the strategy of dividing GZSCC into two groups by HPV status, the predictive model integrating more variables could additionally identify a unique high-risk GZSCC group with the lowest OS rate. CONCLUSIONS: GZSCC patients had distinct clinical characteristics and prognosis compared with OPSCC and OCSCC, integrating HPV status and other clinical factors could help distinguish GZSCC and predict their prognosis.