Clinicopathologic characteristics of HPV-associated head and neck squamous cell carcinoma in Southern China: long-term retrospective study of 400 cases.

Background: Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is an evolving and growing disease, especially in developing countries. However, the clinical characteristics of HPV-associated HNSCC in regard to HPV infection rates, patient features, and prognosis are under-reported in the Asian population. Methods: In this study, we retrospectively enrolled a 400-case cohort of HNSCC with p16 immunochemistry and analyzed with long-term follow-up. We investigate the current HPV prevalence of HNSCC, unique HPV-associated patient clinical characteristics, and patient prognosis in the southern China population. Results: HPV infection exhibited a 15% prevalence in all HNSCC cases, notably higher in oropharyngeal cases (30.7%), followed by oral cavity (11.8%), laryngeal (10.1%), and hypopharyngeal (2.5%). HPV status, gender, old age, and location of tumor were significantly associated with the patient's survival. Tonsil invasion was found more frequent in HPV-positive oropharyngeal HNSCC than in HPV-negative cases. HPV-associated HNSCC patients tend to possess stronger tobacco and alcohol habits, which were correlated to poor survival. HPV status's correlation with gender, age, and anatomical location is associated intricately with patient survival. The secondary primary tumor rate was found higher within the HPV-negative group, compared to the HPV-positive group (9.12% versus 1.67%). Conclusion: Our study provided a current picture of HPV-associated HNSCC in the southern China population and elaborated the understanding of key factors that correlate to HNSCC prognosis. Our findings indicated a strong susceptibility of HPV-associated oropharyngeal HNSCC in the tonsil and the difference in secondary primary tumor rates associated with HPV status.

HPV in head and neck cancer In this study, we retrospectively enrolled a 400-case cohort of HNSCC with p16 immunochemistry and analyzed with long-term follow-up. We investigate the current HPV prevalence of HNSCC, unique HPV-associated patient characteristics, along with patient prognosis in southern China population. Our findings indicated a strong susceptibility of HPV-associated oropharyngeal HNSCC in tonsil and difference of secondary primary tumor associated with HPV status. Our study provided a current picture of HPV-associated HNSCC in southern China population and elaborated the understanding of key factors that correlate to HNSCC prognosis.

Neoadjuvant chemoimmunotherapy shows major pathological response and low recurrence in head and neck squamous cell carcinoma.

BACKGROUND: The study aimed to investigate the efficacy and survival outcomes of neoadjuvant chemotherapy combined with programmed cell death protein 1 (PD-1) blockade (neoadjuvant chemoimmunotherapy) for patients with resectable head and neck squamous cell carcinoma (HNSCC). METHODS: A retrospective analysis was conducted. Patients with initially diagnosed, resectable HNSCCs who received the neoadjuvant chemoimmunotherapy and radical surgery were included. Correlation analysis between patients' clinical characteristics and pathological responses, and survival analysis were performed. RESULTS: A total of 79 patients were included. The majority of patients (55, 69.6%) were diagnosed at locally advanced stages and most of them (58, 73.4%) had tumor located at the oral cavity. Nearly half of patients (35, 44.3%) received two cycles of neoadjuvant chemoimmunotherapy and the rest had three or more cycles. The R0 resection rate was 98.7%. In the pathological evaluation, 53.1% of patients reached pathological complete responses or major pathological responses. After a median follow-up of 17.0 months, the 1-year disease-free survival (DFS) and overall survival (OS) rates were 87.2% and 97.4%, respectively. The pathological response showed a significantly positive association with survival benefits (p < 0.001). Patients with human papillomavirus (HPV)-positive oropharyngeal cancer had the best pathological response and survival outcomes. Besides, history of radiation at head and neck region and poor pathological response were found to be independent risk factors of DFS for patients receiving such treatments. CONCLUSION: Neoadjuvant chemoimmunotherapy of HNSCC showed high rate of pathological response and low recurrence rate, holding promise for becoming the new standard of care for resectable HNSCC.

Analysis of T1-T2 stage oropharyngeal squamous cell carcinoma treated with transoral robotic surgery.

Objective: Transoral robotic surgery (TORS) has become an effective treatment for early-stage oropharyngeal squamous cell carcinomas (OPSCCs). We aimed to analyze the clinical safety and efficacy of TORS for human papilloma virus (HPV)-positive and HPV-negative OPSCC in China. Methods: Patients with OPSCC of pT1-T2 stage who underwent TORS from March 2017 to December 2021 were analyzed. Results: A total of 83 patients (HPV-positive, n = 25; HPV-negative, n = 58) were included. The median age of the patients was 57.0 years and 71 were men. The majority of primary tumor sites were palatine tonsils (52, 62.7%) and base of tongues (20, 24.1%). Three patients have a positive margin. A total of 12 (14.5%) patients received tracheotomies, the average duration of tracheostomy tube use was 9.4 days, and nasogastric tube was 14.5 days. No patient had a long-term tracheotomy. The 3-year overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) for all 83 patients were 89.5%, 80.1%, and 83.3%, respectively. The OS at 3 years between the HPV-positive group and HPV-negative group were 100% versus 84.3% (P = .07), while the DFS and RFS between two groups also showed no significant difference. Among multivariate cox regression analysis of all potential risk factors, smoking was the significant risk factors for disease recurrence (P < .05). Conclusion: Transoral robotic surgery achieved encouraging oncologic outcomes and safety in T1-T2 stage OPSCC treatment, regardless of HPV status. Level of Evidence: 4.

Chinese expert recommendations on management of hepatocellular carcinoma during COVID-19 pandemic: a nationwide multicenter survey.

BACKGROUND: This study aimed to investigate the work status of clinicians in China and their management strategy alteration for patients with hepatocellular carcinoma (HCC) during the COVID-19 pandemic. METHODS: A nationwide online questionnaire survey was conducted in 42 class-A tertiary hospitals across China. Experienced clinicians of HCC-related specialties responded with their work status and management suggestions for HCC patients during the pandemic. RESULTS: 716 doctors responded effectively with a response rate of 60.1%, and 664 were included in the final analysis. Overall, 51.4% (341/664) of clinicians reported more than a 60% reduction of the regular workload and surgeons declared the highest proportion of workload reduction. 92.5% (614/664) of the respondents have been using online medical consultation to substitute for the "face-to-face" visits. Adaptive adjustment for the treatment strategy for HCC was made, including the recommendations of noninvasive and minimally invasive treatments such as transcatheter arterial chemoembolization for early and intermediate stage. Targeted therapy has been the mainstay for advanced stage and also as a bridge therapy for resectable HCC. DISCUSSION: During the COVID-19 pandemic, online medical consultation is recommended to avoid social contact. Targeted therapy as a bridge therapy is recommended for resectable HCC considering the possibility of delayed surgery.

Feingold syndrome type 2 in a patient from China.

Feingold syndrome type 2 (FGLDS2, MIM614326) is a genetic congenital malformation syndrome, caused by germline heterozygous deletion of MIR17HG on chromosome 13q31, which is extremely rare worldwide. To date, less than 25 patients have been described in the literature. Here, we report on a 3-year-old girl presented with hip dysplasia, polysyndactyly of the left thumb, brachymesophalangy of the fifth digit, microcephaly, intellectual disability, and growth delay. This is likely to be the first case of Feingold syndrome type 2 ever discovered among Chinese population. Through genetic testing and pedigree analysis, she was identified to have a de novo 4.8-Mb microdeletion at chromosome 13q31.3-q32.1, encompassing MIR17HG, GPC5, and GPC6. Additionally, we detected two common compound heterozygous variants (c.919-2A>G and c.147C>G) in SLC26A4 encoding pendrin protein, as well as a novel heterozygous variant c.985_988del in COMP encoding cartilage oligomeric matrix protein. This case report aims to analyze the microdeletion and the three types of variant detected in the patient, and to explore the association between the genotype and phenotype in patients with Feingold syndrome type 2, which may contribute to further understanding and future diagnosis of this disorder.

PDCD6 cooperates with C-Raf to facilitate colorectal cancer progression via Raf/MEK/ERK activation.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies, and it's expected that the CRC burden will substantially increase in the next two decades. New biomarkers for targeted treatment and associated molecular mechanism of tumorigenesis remain to be explored. In this study, we investigated whether PDCD6 plays an oncogenic role in colorectal cancer and its underlying mechanism. METHODS: Programmed cell death protein 6 (PDCD6) expression in CRC samples were analyzed by immunohistochemistry and immunofluorescence. The prognosis between PDCD6 and clinical features were analyzed. The roles of PDCD6 in cellular proliferation and tumor growth were measured by using CCK8, colony formation, and tumor xenograft in nude mice. RNA-sequence (RNA-seq), Mass Spectrum (MS), Co-Immunoprecipitation (Co-IP) and Western blot were utilized to investigate the mechanism of tumor progression. Immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) were performed to determine the correlation of PDCD6 and MAPK pathway. RESULTS: Higher expression levels of PDCD6 in tumor tissues were associated with a poorer prognosis in patients with CRC. Furthermore, PDCD6 increased cell proliferation in vitro and tumor growth in vivo. Mechanistically, RNA-seq showed that PDCD6 could affect the activation of the MAPK signaling pathway. PDCD6 interacted with c-Raf, resulting in the activation of downstream c-Raf/MEK/ERK pathway and the upregulation of core cell proliferation genes such as MYC and JUN. CONCLUSIONS: These findings reveal the oncogenic effect of PDCD6 in CRC by activating c-Raf/MEK/ERK pathway and indicate that PDCD6 might be a potential prognostic indicator and therapeutic target for patients with colorectal cancer.

Clinical Analysis of 15 Cases of Gallbladder Neuroendocrine Carcinoma and Comparison with Gallbladder Adenocarcinoma Using a Propensity Score Matching.

PURPOSE: This study aimed to investigate the clinicopathological features and prognosis of gallbladder neuroendocrine carcinoma (GB-NEC). PATIENTS AND METHODS: Fifteen patients with GB-NEC and 171 patients with gallbladder adenocarcinoma (GB-ADC) treated in two tertiary medical centers between 2009 and 2015 were included. The clinicopathological features and prognostic risk factors of GB-NEC were analyzed retrospectively. A propensity score matching in a 1:2 ratio was used to compare the prognosis of GB-NEC and GB-ADC. RESULTS: For patients with GB-NEC, the median age of patients was 58.4 years (range 26-75), with a M:F ratio of 7:8. Based on 2010 WHO classification, ten cases were pathologically confirmed as NECs and five cases as MANECs. For TNM staging, eleven patients were stage III or above; while for Nevin staging, seven patients were stage IV or above. The 1-, 2-, and 3-year overall survival (OS) of GB-NEC were 60.0%, 38.8% and 31.1%, respectively, and the median survival time was 20.4 months. Patients with lymph node metastasis had significantly shorter survival than those without (OS: 10.4 vs 26.0 months, p<0.05). Accordingly, patients of Nevin stage III had better OS than those of Nevin stage IV (p<0.05), but other potential risk factors including gender, age, clinical symptoms, TNM stage, histopathologic subtype and treatment showed no significance. After the propensity score matching, the baseline variables had no significant difference between 15 patients with GB-NEC and 30 patients with GB-ADC, survival analysis showed GB-NEC had worse prognosis (3-year overall survival rate: 31.1% vs 63.8%, p<0.01). CONCLUSION: Nevin staging helps classify patients of GB-NEC with different prognosis and the lymph node metastasis is a strong negative prognostic factor for OS. The propensity score analysis revealed even with the similar stage and treatment, GB-NEC still had worse OS than GB-ADC.

Current situation and trends of online academic activities for oncologists during the COVID-19 pandemic: a multicenter survey.

BACKGROUND: The present study aimed to investigate the current situation and future trends of online academic activities for oncologists during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: From April 22 to May 5, 2020, a multicenter survey was conducted using an online questionnaire platform. To compare categorical variables, χ2-test, the kappa consistency analysis, and Wilcoxon rank sum test were applied. For all statistical hypotheses, P<0.05 was considered significant. RESULTS: In the present study, 2,120 oncologists participated in the survey. Of these, 2,035 respondents participated in online academic activities. During the pandemic, online academic activities significantly increased [oncologists who participated in online academic activities ≥60%: 64.58% (during the pandemic) vs. 10.90% (before the pandemic), Cohen's kappa coefficient =0.0499, P<0.001]. The findings indicated that 90.6% of respondents considered that the online academic activities would become a future trend. The main reason for the increase in online academic activities was due to in-person academic conferences and diagnoses/treatment being affected by the pandemic. Both speakers/chairs and audiences agreed that online academic activities resulted in reduced stress (61.15% vs. 67.26%, respectively; χ2=7.009, P=0.03). In the present study, 62.21% of audiences considered that the recording function of online activities was very important (score 5), while only 53.86% of the speakers had the same opinion (Z=-3.5340, P<0.001). Compared with provincial capital cities and other cities, the participants from first-tier cities thought that online academic activities required significant physical energy (χ2=6.41, P=0.040), and were more reluctant for the playback of activity contents (χ2=9.33, P=0.002) and the screenshot of activity contents (χ2=41.99, P<0.001). CONCLUSIONS: During the COVID-19 pandemic, online academic activities have become the main form of academic exchanges for oncologists. Taking full advantage of online academic activities and paying adequate attention to the participants' requirements with different roles and titles, and from different cities, are key to improving the quality of and involvement in online academic activities.

Value of computed tomography evaluation in pathologic classification and prognosis prediction of gastric neuroendocrine tumors.

BACKGROUND: The study aims to investigate the correlation of CT characteristics with pathological classifications and the prognostic value of CT features in patients with gastric neuroendocrine neoplasms (g-NENs). METHODS: Ninety-one cases of pathologically diagnosed g-NENs, including 15 cases of well-differentiated neuroendocrine tumors (NETs) (G1 and G2) and 76 cases of poor-differentiated neuroendocrine carcinomas (NECs) (G3 and MANEC) were retrospectively studied. All cases were included in correlation analysis of CT characteristics with pathologic grades. Among them, 76 patients who had fulfilled follow-up data were included for overall survival (OS) and disease-free survival (DFS) analysis. RESULTS: CT characteristics that favor poor differentiation include tumor location (fundus and cardia), larger tumor size (>3.0 cm), infiltrative growth, unclear tumor margin, serosa involvement, ulceration and lymph node metastasis (P<0.05). Most variables had sensitivities >80% and specificities >60% to distinguish NECs from NETs. Through log-rank analysis, it was revealed that serosa involvement, cystic degeneration, necrosis, heterogeneous enhancement and lymph node metastasis led to worse DFS and OS for patients with g-NENs (P<0.05). COX regression analysis showed that serosa involvement and lymph node metastasis were independent risk factor for DFS and OS, respectively, despite of grading, staging and therapeutic choices (P<0.05). Moreover, high Ki-67 index (>55%) in G3 g-NENs is in correlation with serosa involvement and lymph node metastasis; accordingly, patients with higher Ki-67 index had worse 1-year DFS (61.7% vs. 92.3%; P<0.05). CONCLUSIONS: CT characteristics can be useful discriminators and prognostic factors for g-NENs and may help identify G3 g-NEC from G3 g-NEN by revealing its poor differentiation and high invasive potential.

The safety and feasibility of a single incision in simultaneous resection for patients with colorectal cancer liver metastases.

BACKGROUND: The approach of performing a simultaneous resection for patients with colorectal cancer liver metastases has been lauded universally, but the operation procedures have differences. In general, colorectal lesions are removed laparoscopically; however, some liver metastases cannot be resected under laparoscopy. For these patients, the traditional approach of performing a simultaneous resection which utilizes the inferior abdominal midline incision and the right subcostal incision is preferred. In this study, we assessed the safety and feasibility of the single right subcostal incision approach for patients with either rectal or sigmoid colon cancer and liver metastasis who underwent simultaneous resection. METHODS: A total of 85 patients with rectal or sigmoid colon cancer and liver metastases who underwent simultaneous resection from January 2012 to December 2016 in the Cancer Hospital Chinese Academy of Medical Sciences were identified. Clinicopathological data, as well as operative and perioperative outcomes, were collected and analyzed retrospectively. RESULTS: Overall, 42 patients were included in this study, 26 (61.9%) patients underwent simultaneous resection with a single surgical incision (right subcostal incision), and 16 (38.1%) underwent simultaneous resection with dual surgical incisions (inferior abdominal midline incision and right subcostal incision). Compared to the dual-incision approach, the single-incision approach had a shorter operation time (328.0 vs. 420.0 min, P=0.006) but had no significant differences in total hospitalization time, postoperative hospitalization time, intraoperative blood loss, time of postoperative drainage tube extraction, time to the first postoperative bowel movement, and postoperative complications (P>0.05). CONCLUSIONS: The single-incision approach (right subcostal incision) is feasible and safe for patients with either sigmoid colon or rectal cancer and liver metastases.