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Purpose: This study aims to examine the role of elective nodal irradiation (ENI) in clinically node-negative (cN0) sinonasal squamous cell carcinoma (SNSCC) and to define the optimal radiation fields for ENI., Methods and Materials: We retrospectively reviewed 368 patients with cN0 SNSCC treated between 2009 and 2021. The study evaluated the impact of ENI on overall survival, progression-free survival, regional failure-free survival, and distant metastasis-free survival, along with the coverage areas of ENI., Results: The majority of patients underwent surgery (316/368, 85.9%), with 276 of 368 (75%) having tumors in the maxillary sinus or nasal cavity and 249 of 368 (67.7%) presenting with T4 disease. Additionally, in 119 of the 368 cases (32.3%), tumors were poorly differentiated. The 5-year overall survival, progression-free survival, regional failure-free survival, and distant metastasis-free survival rates were 59.3%, 54.0%, 57.6%, and 58.8%, respectively. ENI was performed in 217 patients (59%), with 16 experiencing neck relapse during follow-up. Although ENI did not enhance survival rates, it significantly reduced the overall regional failure rate (7.9% vs 1.8%; χ 2 = 7.98; P < .01) and the cumulative incidence of regional failure (P = .045). Additionally, the subgroups with maxillary sinus origin (2.3% vs 13.5%; P = .025), T4 stage (1.8% vs 8.5%; P = .028), and poor differentiation (2.4% vs 13.5%; P = .029) had higher cumulative incidences of regional failure in patients without ENI. No significant difference was observed in survival and regional failure rates between patients treated with ENI to levels Ib and II with or without level III, as well as between cN0 patients with nonmidline crossing lesions receiving unilateral or bilateral ENI., Conclusions: Despite no survival benefit, ENI significantly decreases the regional failure rate in patients with cN0 SNSCC. For primary lesions not crossing the midline, ipsilateral ENI targeting levels Ib and II proves to be an effective strategy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Retinoic acid receptor-related orphan receptor alpha (RORα), an essential tumor suppressor in a range of human malignancies, is classified as a member of the orphan nuclear receptor family. The most prevalent form of oral cancer, tongue squamous cell carcinoma (TSCC) is characterized by its severe malignancy and unfavorable prognosis. However, the extent to which its tumorigenesis mechanisms are associated with RORα expression levels is still not fully understood. The objective of this study was to examine the molecular mechanisms by which RORα is involved in TSCC. Through the use of immunohistochemistry (IHC), it was discovered that the expression level of RORα was significantly downregulated in TSCC tissues when compared to adjacent normal tissues in this study. To further investigate the role of RORα in TSCC, we activated the expression of RORα in human TSCC cell line (SCC9 cells) by transfecting RORα cDNA and using the selective RORα agonist SR1078. The results show that RORα can significantly inhibit the invasion, migration, proliferation, and adhesion of TSCC cells and induce cell apoptosis. In addition, xenograft models confirmed the conclusion that stable activation or treatment with SR1078 to increase RORα content significantly inhibited tumor growth and development. Taken together, this study provides solid evidence for the inhibitory role of RORα in the progression of TSCC. In addition, the preliminary application results of SR1078 in TSCC show that SR1078 is expected to be a potential therapeutic medication for TSCC. These findings provide innovative perspectives on the development of potential biomarkers and agents for TSCC therapy. The objective is to introduce novel strategy and alternatives for the prevention and treatment of TSCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate the clinicopathological features, molecular pathology characteristics, and prognosis of non-small cell lung carcinoma (NSCLC) exhibiting co-expression of p40 and thyroid transcription factor1 (TTF1). Methods: Clinical and pathological data of six NSCLC cases with co-expression of p40 and TTF1 diagnosed at the First People's Hospital of Xiaoshan District, Hangzhou, China from January 2016 to December 2023 were collected. Relevant literature was also reviewed. Results: NSCLC with co-expression of p40 and TTF1 commonly occurred in male smokers and had been in stage Ⅲ-Ⅳ when diagnosis. Microscopic examination revealed that the tumor cells were arranged in solid nests and sheets with marked atypia and visible mitotic figures. There was no prominent evidence of keratinization or glandular formation. The tumor cells diffusely co-expressed p40 and TTF1, exhibiting a dual immunophenotype characteristic of both squamous cell carcinoma and adenocarcinoma. Molecular testing of four NSCLC co-expressing p40 and TTF1 revealed the presence of common EGFR mutations, as well as mutations of NRAS (mutation rate of 2.09%), EML4-ALK (mutation rate of 24.77%), and PIK3CA (exon 10 c.1658 G>C p.S553T, mutation rate of 4.32%). All six tumors were poorly differentiated, highly invasive, and associated with poor prognosis. Four of the six patients experienced widespread metastasis and died within 7 to 30 months after the diagnosis or initial treatment. Conclusions: NSCLC with co-expression of p40 and TTF1 exhibits distinct clinicopathological features, immunophenotypes, molecular alterations, and clinical outcomes, characterized by rapid progression and poor prognosis. Pathologists should be vigilant in recognizing this entity to avoid misdiagnosis and missed diagnosis.

Laryngeal squamous cell carcinoma (LSCC) is a common cancer with high mortality and tumor mutation burden (TMB), and high TMB is associated with favorable survival. The expression, mutation, and survival data were obtained from The Cancer Genome Atlas database. The mutation and differentially expressed genes were analyzed using limma R package. The function enrichment was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. TMB-related genes were identified by Weighted correlation network analysis. Univariate, multivariate and Lasso cox analyses were used to determine hub genes. The risk model and mRNA expression was validated by Receiver Operating Characteristic curve and qRTPCR. The immune infiltration was analyzed by xCELL. The drug sensitivity was determined through gene set cancer analysis database. We identified 1129 differentially expressed genes related to TMB. Enrichment analysis showed they were associated with immune response. ANKLE1 and PPP1R14A were screened out as hub genes. Receiver Operating Characteristic curve identified that the risk model had an effective prognosis value in progression-free interval of LSCC. Immune infiltration levels of 16 immune cells were significantly changed in high risk score group compared with low risk score group. ANKLE1 and PPP1R14A expressions were significantly upregulated in tumor group, which was consistent with qRTPCR results, and associated with better prognosis. ANKLE1 was negatively related to many drug sensitivities, while PPP1R14A was positively related to some drug sensitivities. We constructed an effective risk model constructed by ANKLE1 and PPP1R14A which was related to TMB in LSCC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: WNT7B is a glycoprotein that plays a crucial role in tumorigenesis. This study aimed to investigate the role of WNT7B in oral squamous cell carcinoma (OSCC)., Methods: Bioinformatic databases, immunohistochemistry, a real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to detect WNT7B expression in OSCC. The clinical and prognostic importance of WNT7B expression was evaluated. WNT7B expression was examined in oral leukoplakia and carcinoma induced by 4-nitroquinoline 1-oxide in mice. Loss- and gain-of-function analyses were performed to elucidate the role of WNT7B in OSCC cells. Subcutaneous tumor model was established to observe the effects of WNT7B on tumor growth. Co-Immunoprecipitation was used to explore the Frizzled receptors that WNT7B may bind to., Results: WNT7B upregulated in OSCC and associated with lymph node metastasis, perineural invasion, and an unfavorable prognosis in patients with OSCC. A gradual increased in WNT7B expression during the malignant progression of OSCC. WNT7B promoted cell proliferation, migration, invasion, while silencing WNT7B abolished these effects. Knocking down the expression of WNT7B inhibits tumor growth in vivo. WNT7B functions by binding to the Frizzled 7 receptor and facilitates the nuclear translocation of β-catenin., Conclusions: WNT7B contributes to the progression of OSCC by modulating the WNT/β-catenin signaling pathway. These findings highlight the potential of WNT7B as a novel prognostic biomarker and promising therapeutic target for OSCC., (© 2024. The Author(s).)

Objectives: To ascertain the prognostic role of the expression levels of estrogen receptor (ER) and progesterone receptor (PR) within the stroma microenvironment of cervical cancer and explore their correlation with clinical parameters., Materials and Methods: This retrospective cohort study involved patients with cervical cancer diagnosed and treated at Hualien Tzu Chi Hospital between 2000 and 2010. ERα, PRB, and PR (A + B) expression levels in 169 cervical carcinoma samples, including both the tumor and stromal components, were independently scored by two pathologists, and survival and clinicopathological parameters were analyzed., Results: ERα or PRs were predominantly expressed in the stromal compartment rather than within cervical cancer cells. Their expression was observed comprehensively within the intra- and peritumor stroma cells. A stromal PRB expression significantly correlated with a lower 5-year mortality because of cervical cancer (p = 0.011). Particularly, levels of both stromal ERα and PRB expressions correlated with lower hematogenous distant metastase rates (p = 0.013 and p = 0.011, respectively). In the multivariable logistic regression analyses, stromal PRB independently conferred a lower risk of 5-year mortality (p = 0.022), regardless of age, histology, International Federation of Gynecology and Obstetrics (FIGO) stage, tumor differentiation, lymphovascular space invasion, and lymphatic and hematogenous metastases. Moreover, the incorporation of stromal PR (A + B) and PRB expression in the FIGO stage significantly enhanced the accuracy of survival prediction., Conclusion: Stromal PRB expression emerges as an independent and favorable prognostic marker for cervical squamous cell carcinoma and correlated with a low risk of hematogenous metastases. The findings imply that incorporating this marker into the FIGO stage better predicts the survival for cervical cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Tongue cancer at a young age demonstrates an increase in incidence, aggressiveness, and poor response to therapy. Classic etiological factors for head and neck tumors such as tobacco, alcohol, and human papillomavirus are not related to early-onset tongue cancer. Mechanisms of development and progression of this cancer remain unclear. In this study, we performed spatial whole-transcriptome profiling of tongue cancer in young adults compared with older patients. Nine patients with tongue squamous cell carcinoma (T2-3N0-1M0) were included and divided into two groups: younger (n = 5) and older than 45 years (n = 4). Formalin-fixed paraffin-embedded (FFPE) and fresh frozen (FF) samples of tumor tissue from 4 young and 5 older patients, respectively, were used for spatial transcriptomic profiling using the 10 × Genomics Visium. The findings were validated using SeekGene single cell full-length RNA sequencing (1 young vs 1 older patient) and TCGA data (15 young vs 70 older patients). As a result, we performed the first successful integration of spatial transcriptomics data from FF and FFPE samples and revealed distinctive features of tongue cancer in young adults. Oxidative stress, vascular mimicry, and MAPK and JAK-STAT pathways were enriched in early-onset tongue cancer. Tumor microenvironment demonstrated increased gene signatures corresponding to myeloid-derived suppressor cells, tumor-associated macrophages, and plasma cells. The invasive front was accompanied by vascular mimicry with arrangement of tumor-associated macrophages and aggregations of plasma cells and lymphocytes organized into tertiary lymphoid structures. Taken together, these results indicate that early-onset tongue cancer has distinct transcriptomic features and molecular mechanisms compared to older patients., (© 2024. The Author(s).)

Background/aim: Pleomorphic high-grade squamous intraepithelial lesions (PHSILs) of the uterine cervix are characterized by strikingly pleomorphic and enlarged nuclei with brisk mitotic activity. The aim of this study was to analyze the clinical outcomes of patients with PHSIL., Patients and Methods: Clinical data were collected from the electronic medical records of 44 patients with PHSIL., Results: The patients' mean age was 52.1 years. The initial cytological diagnosis was HSIL in 43.2% of patients. High-risk human papillomavirus was detected in 89.5% of patients. The human papillomavirus type was not predominated by one specific type. The patients were treated with conization alone or with conization with subsequent hysterectomy. Two cases of squamous cell carcinoma coexisting with PHSIL, and one case of adenoid basal carcinoma were detected among the surgical specimens. Follow-up cytology revealed negative results for intraepithelial lesions in all patients, except for one patient who experienced recurrent PHSIL 41 months after hysterectomy and underwent laser ablation., Conclusion: The incidence rates of concurrent squamous cell carcinoma (4.5%) and recurrence (2.3%) in our PHSIL cohort were lower than those previously reported in patients with conventional HSIL. Our findings suggest that pleomorphic nuclear change alone in PHSIL was not associated with worse clinical outcomes than conventional HSIL and support the notion that PHSIL does not require more aggressive clinical management than conventional HSIL. However, close follow-up with cytological examination may be necessary to determine the potential risk of recurrence., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Human papillomavirus-independent (HPVI) squamous cell carcinoma (SCC) and adenosquamous carcinoma (ASC) of the uterine cervix are extremely rare. The aim of this study was to comprehensively describe the clinicopathological features, patient outcomes, and immunophenotypes of HPVI SCC and ASC., Patients and Methods: We found four and two patients with HPVI SCC and ASC, respectively, and reviewed their electronic medical records and pathology slides. We also performed immunostaining for p16 and p53., Results: All except one patient underwent surgery. Two, one, and one patients with HPVI SCC were diagnosed as having IIIC1, IVA, and IVB diseases, respectively. Two patients with HPVI SCC experienced recurrences, and died of disease within nine months after treatment initiation. Both patients with HPVI ASC developed lung metastasis at four months post-operatively. HPVI SCCs and the squamous component of HPVI ASCs showed keratinizing, condylomatous, or poorly differentiated morphology. The glandular component of HPVI ASCs was gastric-type endocervical adenocarcinoma. None of the six tumors exhibited block positivity for p16. Two HPVI SCCs and one HPVI ASC displayed aberrant p53 expression., Conclusion: HPVI SCC is a rare and aggressive cervical malignancy that presents initially as advanced-stage disease with poor prognosis. Although the patients with initial stage I and II HPVI ASC were treated with curative intent, distant metastases appeared in the lungs during the early course of treatment. Further investigations are necessary to clarify the association between histological features and clinical behavior of HPVI ASC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to assess the impact of hypoxia on epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinoma (HNSCC), focusing on the involvement of transcription factors hypoxia inducible factor 1 (HIF-1α) and Jumonji Domain-Containing Protein 1A (JMJD1A)., Materials and Methods: FaDu and Cal33 cell lines were subjected to hypoxic and normoxic conditions. Cell proliferation was quantified electronically, while PCR and western blot analyses were used to measure mRNA and protein levels of HIF-1α, JMJD1A, and EMT markers. EMT was further characterized through immunofluorescence, migration, and invasion assays., Results: Hypoxic conditions significantly reduced cell proliferation after 48 hours in both cell lines. HIF-1α mRNA levels increased initially during short-term hypoxia but declined thereafter, while JMJD1A mRNA levels showed a sustained increase with prolonged hypoxia. Western blot analysis revealed contrasting trends in protein levels. EMT marker expression varied markedly over time at both the mRNA and protein levels, suggesting EMT induction in hypoxia within 24 hours. Immunofluorescence, migration, and invasion assays supported these findings., Conclusion: The study provides evidence of hypoxia-induced EMT in HNSCC, although conflicting results suggest a complex interplay among molecular regulators involved in this process., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Esophageal carcinomas comprise 2 entities, squamous cell carcinoma and adenocarcinoma, which differ in pathogenesis and treatment. Elimination of inflammatory influences and risk factors, such as obesity and gastroesophageal reflux that contribute to a rising incidence of adenocarcinoma, is crucial for tumor prevention. In Germany, general endoscopic screening for upper GI tumors is not recommended, whereas endoscopic surveillance is applied in the presence of Barrett's metaplasia. In the future, better prediction models will be needed to identify patients at risk who will benefit from endoscopic surveillance. Precancerous lesions and early tumor stages can be removed endoscopically using modern resection methods. In recent years, therapeutic strategies for advanced esophageal tumors have undergone significant changes. In the multimodal treatment of locally advanced stages, radiochemotherapy remains to play a key role for squamous cell carcinoma, whereas new evidence highlights the importance of perioperative chemotherapy for the optimal management of adenocarcinoma. Systemic treatment options for both tumor entities have been significantly expanded due to the successful use of immune checkpoint inhibitors in adjuvant and palliative treatment regimen. Determination of PD-L1 and MSI status has therefore become decisive for the choice of therapy. In metastatic stages of adenocarcinoma, chemotherapy can now be supplemented by multiple antibodies directed against Her2, PD1, or claudin 18.2, and the antibody-drug conjugate trastuzumab deruxtecan has become a Her2-targeted option in second line treatment., Competing Interests: Decker: Keine Interessenkonflikte; Quante: Advisory Board für MSD, BMS, Astella, AstraZeneca, (Thieme. All rights reserved.)

SMARCB1/SMARCA4-deficient malignancies of the female genital tract are rare entities, characterized by similar histologic features, such as sheet-like growth patterns and rhabdoid cells. Previous studies have shown mutually exclusive loss of SMARCA4/BRG1 and SMARCB1/INI1. Herein, we describe a unique cervical mixed carcinoma in a 77-year-old patient. The tumor consisted of 3 components, gastric-type adenocarcinoma, squamous carcinoma, and undifferentiated carcinoma. While the undifferentiated carcinoma was negtive for CK7, CK5/6 and p63, it was positive for pan-CK. DNA-based next-generation sequencing revealed a nonsense mutation in SMARCA4, copy number loss in SMARCB1, and a nonsense mutation in ARID1A. Different molecular alterations of the switch/sucrose nonfermenting complex subunits in the present case may provide further insights into the functions of the switch/sucrose nonfermenting complex in the progression of tumors., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Background: This retrospective study investigates the clinicopathological features and outcomes of young and elderly patients diagnosed with lip squamous cell carcinoma (LSCC)., Material and Methods: Data from LSCC patients from Dr. Luiz Antonio Hospital in Natal, Brazil (2000-2015) were analyzed, grouping individuals below 40 and above 60 years old. Demographics, lifestyle habits, clinicopathologic characteristics, and treatment outcomes were examined using descriptive statistics, Chi-square and Fisher's tests, and Kaplan-Meier survival analysis., Results: A total of 47 patients was analyzed, being 20 younger and 27 older, finding significant age-related differences (p = < 0.0001). Although in both groups the tumor was more common in males, older patients had a higher rate of females (29.6%) (p=0.0358) and smoking (70.4%) (p = 0.0043) and underwent more modalities of treatments (p = 0.0027). There were no significant differences in the other analyzed clinicopathologic factors, and survival rates did not differ significantly, though younger patients showed slightly better survival metrics in univariate analysis., Conclusions: LSCC exhibits some distinct clinicopathological features across different age groups, with significant differences in treatment modalities and progression rates. Age-specific approaches may be required to optimize treatment outcomes.

Background: In the FIGO 2018 classification, women with cervical cancer and a depth of invasion ≤ 5 mm and a horizontal spread of > 7 mm in excisional biopsy with tumour-free margins, are now classified as stage IA instead of IB. This stage shift may reduce the likelihood of surgical lymph node staging. It is therefore crucial to estimate the risk and risk factors of lymph node metastasis (pN+) in this group., Methods: Women diagnosed with cervical cancer between 2005 and 2022 were identified from nationwide population-based registries from the Netherlands, Denmark, and Sweden. Inclusion criteria were squamous cell carcinoma or adenocarcinoma, FIGO 2009 stage IB1, a depth of invasion ≤ 5 mm and horizontal spread of > 7-≤ 40 mm. All cases underwent radical hysterectomy or radical trachelectomy, and surgical lymph node staging. Logistic regression was used to identify risk factors of pN+., Results: We included 992 women (pN+ 4.1 %; n = 41). Lymphovascular space invasion (LVSI) was a significant risk factor of pN+ (odds ratio 4.26, 95 % confidence interval 2.24-8.32). Accordingly, the risk of pN+ was ≥ 7.3 % in LVSI-positive tumours. The risk was lowest in LVSI-negative tumours with a size of > 7-≤ 20 mm (2.2 %), although this varied by depth of invasion and histological subtype (pN+ range 0.6-5.1 %)., Conclusion: Women with LVSI-positive FIGO 2018 IA cervical cancer and a horizontal spread > 7 mm, should undergo surgical lymph node staging. In LVSI-negative tumours, lymph node staging should not be routinely performed; tumour size, depth of invasion and histology should be considered., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HF: Board Member Surgical Science, PJ: MSD Advisory Board for cervical cancer, All other authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths in developing countries. The oral tongue is the most common site involved by OSCC. About one-third of the patients have neck nodal metastasis at presentation. Oral tongue reconstruction after resection for cancer is necessary for proper rehabilitation. For patients who are medically unfit for prolonged surgery like a free tissue transfer, local flaps are employed for tongue reconstruction. The submental flap is a popular option. However, when there is an extensive floor of mouth involvement or bulky nodal disease in ipsilateral level 1, submental flap harvesting based on contralateral facial vessels is possible without compromising oncological safety. This study discusses the feasibility and outcomes of contralateral submental artery island flap (SMIF) for reconstruction after resection of oral tongue carcinoma in a retrospective series of 34 patients followed up for a median of 8.5 months., Results: Of the 34 oral tongue cancer patients in the study, 16 had neoadjuvant chemotherapy before surgery. Thirty-three underwent bilateral neck dissection. Two patients had partial flap loss, which was managed conservatively. Five patients had either locoregional or distant recurrence, but none in the flap site. Three had pathological positive nodes at ipsilateral level 1b, and one had pathologically positive nodes at contralateral level 1b. Tongue motility and speech intelligibility were satisfactory on follow-up., Conclusion: In the properly selected patient, contralateral SMIF offers an oncologically safe and technically simpler alternative for free flap reconstruction., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Abstract: Bruton tyrosine kinase (BTK) inhibitors have become an important therapeutic option in treating B-cell malignancies including non-Hodgkin lymphoma and chronic lymphocytic leukemia. However, a noted morbidity associated with their use is the potential for the development of second primary malignancy related to immunomodulation. In this case, we report a second primary malignancy of ocular surface squamous neoplasia (OSSN) owing to BTK therapy. The OSSN was successfully treated and has been monitored without recurrence. To our knowledge, this is the first case of OSSN secondary to BTK therapy., Competing Interests: The author has no funding or conflicts of interest to disclose., (Copyright © 2024 Contact Lens Association of Ophthalmologists.)

Purpose: The assessment of p16INK4a (p16) in oropharyngeal squamous cell carcinoma (OPSCC) has been incorporated into tumor classification, as p16 has been shown to impact survival probability. However, a recent study demonstrated that human papillomavirus (HPV) status in addition to p16 may have a better discriminatory effect on survival probability. This study aims to determine the impact of combined evaluation of p16 and HPV on prognosis., Methods: This was a multicenter, multinational analysis including retrospective and prospective cohorts of patients treated for primary OPSCC with curative intent, based on the data of the HNCIG-EPIC study. The primary outcome was to determine how the combined assessment of HPV and p16 status predicts prognosis of patients with OPSCC compared to p16 assessment alone. We employed multivariable analyses models to compute hazard ratios regarding survival. Analyses were stratified by stage, smoking status, and sub-anatomical region., Results: The study included 7654 patients, with approximately half of the tumors being p16-negative (50.3 %, n = 3849). A total of 9.2 % of patients had discordant p16 and HPV status (n = 704). HPV status significantly impacted overall survival and disease-free survival regardless of p16 status and across both UICC 8th stage I-II and III-IVb cancers. p16-positive/HPV-positive OPSCC patients exhibited the best survival probability., Conclusion: The detection of HPV had a significant impact on survival probability for OPSCC patients with both p16-positive and p16-negative tumors. HPV testing should be integrated in cancer staging, especially in regions of low attributable fraction, alongside p16 evaluation to ensure a comprehensive assessment of prognosis., Competing Interests: Declaration of Competing Interest JPK receiving honoraria from MSD, Merck and BMS; research funding from MSD. No other authors have any conflict of interests to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Previous studies have revealed the importance of CYFRA 21-1 in the diagnosis of oral squamous cell cancer (OSCC). However, the results are inconsistent. This meta-analysis is to evaluate CYFRA 21-1's efficacy in distinguishing OSCC., Methods: Systematic searches of Web of Science, PubMed, and CNKI (1996-2024) were conducted following the Preferred Reporting ltems for Systematic Reviews and Meta-Analyses (PRISMA) guidelines., Results: Analysis of 693 patients and 548 controls yielded combined sensitivity (SEN) of 0.71 (95% CI: 0.68, 0.75), specificity (SPE) of 0.88 (95% CI: 0.85, 0.90), and area under the curve (AUC) of 0.927. Subgroup analysis showed higher SEN (0.88), SPE (0.93), and AUC (0.962) in saliva versus serum. Enzyme-linked immunosorbent assay (ELISA) demonstrated superior performance over electrochemiluminescent immunoassay (ECLIA) (AUC: 0.968 vs. 0.868)., Conclusion: CYFRA 21-1 is effective in OSCC diagnosis, with ELISA showing better sensitivity. Saliva emerges as a promising diagnostic medium compared to serum., Registration: PROSPERO CRD42024566835.

Platinum-based chemotherapy is the first-line treatment for tongue squamous cell carcinoma (TSCC), but most patients rapidly develop resistance. Circular RNAs (circRNAs) are a class of critical regulators in the pathogenesis of several tumors, but their role in cisplatin resistance in TSCC has not been fully elucidated. Here we found that circMAPKBP1 was enriched in cisplatin resistant TSCC cells and was closely associated with enhanced autophagic activity. Functionally, silencing circMAPKBP1 significantly restored the chemosensitivity of cisplatin-resistant TSCC cells both in vitro and in vivo by suppressing autophagy. Mechanistically, circMAPKBP1 enhanced cisplatin sensitivity through the miR-17-3p/TGFβ2 axis by activating autophagy pathway. Data from clinical studies revealed that high expression of circMAPKBP1 and TGFβ2 was closely linked to a poor outcome in TSCC patients. We thus concluded that circMAPKBP1 is a tumor promoting factor and confers cisplatin sensitivity by activating the miR-17-3p/TGFβ2 axis-mediated autophagy. We propose that circMAPKBP1 may be a potential therapeutic target for TSCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Aim: The aim of this study was to assess whether the use of sentinel lymph node (SLN) in addition to lymphadenectomy was associated with survival benefit in patients with early-stage cervical cancer., Methods: International, multicenter, retrospective study., Inclusion Criteria: cervical cancer treated between 01/2007 and 12/2016 by surgery only; squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, FIGO 2009 stage IB1-IIA2, negative surgical margins, and laparotomy approach. Patients undergoing neo-adjuvant and/or adjuvant treatment and/or with positive para-aortic lymph nodes, were excluded. Women with positive pelvic nodes who refused adjuvant treatment, were included. Lymph node assessment was performed by SLN (with ultrastaging protocol) plus pelvic lymphadenectomy ('SLN' group) or pelvic lymphadenectomy alone ('non-SLN' group)., Results: 1083 patients were included: 300 (27.7 %) in SLN and 783 (72.3 %) in non-SLN group. 77 (7.1 %) patients had recurrence (N = 11, 3.7 % SLN versus N = 66, 8.4 % non-SLN, p = 0.005) and 34 (3.1 %) (N = 4, 1.3 % SLN versus N = 30, 3.8 % non-SLN, p = 0.033) died. SLN group had better 5-year disease-free survival (DFS) (96.0 %,95 %CI:93.5-98.5 versus 92.0 %,95 %CI:90.0-94.0; p = 0.024). No 5-year overall survival (OS) difference was shown (98.4 %,95 %CI:96.8-99.9 versus 96.8 %,95 %CI:95.4-98.2; p = 0.160). SLN biopsy and lower stage were independent factors associated with improved DFS (HR:0.505,95 %CI:0.266-0.959, p = 0.037 and HR:2.703,95 %CI:1.389-5.261, p = 0.003, respectively). Incidence of pelvic central recurrences was higher in the non-SLN group (1.7 % versus 4.5 %, p = 0.039)., Conclusion: Adding SLN biopsy to pelvic lymphadenectomy was associated with lower recurrence and death rate and improved 5-year DFS. This might be explained by the lower rate of missed nodal metastasis thanks to the use of SLN ultrastaging. SLN biopsy should be recommended in patients with early-stage cervical cancer., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Abu-Rustum received research funding paid to the institution from GRAIL. Memorial Sloan Kettering Cancer Center also has equity in GRAIL. All remaining authors have declared no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To investigate the failure patterns based on precision radiation treatment and to determine the predictive factors of treatment failure for sinonasal squamous cell carcinoma (SNSCC) patients., Methods: This was a retrospective study that included 214 cases of treatment failure from 441 consecutive patients. Two experienced radiation oncologists evaluated the tumour volume of cases with local recurrence. The 5-year overall survival (OS), progression-free survival (PFS) rates, and distant-metastasis-free survival (DMFS) were estimated. Investigations were performed on the factors that predicted local failure or distant metastasis., Results: About 140 (31.7%) patients developed local recurrence, 24 (5.4%) experienced regional failure, and 65 (14.7%) underwent distant metastasis. In-field, marginal, and out-of-field failures occurred in 55.7% (78/140), 33.6% (47/140), and 10.7% (15/140) of patients with local recurrence, respectively. In logistic regression analysis, factors statistically significant for total local failure included treatment mode (P < .01), chemotherapy (P < .01), and surgical margins (P < .01). Primary tumours with poor differentiation (P = .018) and R2 resection margin (P = .009) were more prone to develop distant failure. The 5-year OS, PFS, and DMFS rates were 57.8%, 52.0%, and 56.7% for the whole cohort. In univariate and multivariate analysis, the skull base involvement was an independent predictor for poorer OS and PFS; orbital invasion was an independent predictor for poorer OS., Conclusions: Local recurrence and distant metastasis were the most common failure modes. Treatment mode, chemotherapy, and surgical margins were related to local recurrence. Poor differentiation and R2 resection margin were predictors for distant failure., Advances in Knowledge: Local recurrence is the most common failure pattern in patients with SNSCC who accepted chemoradiotherapy, and marginal and out-of-field failures occurred in 44.3% of patients with local recurrence., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The survival outcomes of Stage IIIC1 in FIGO 2018 showed significant heterogeneity and it seems unreasonable to administer a uniform treatment regimen for Stage IIIC1 patients. This study aimed to assess the survival outcomes among patients with locally advanced cervical cancer based on various lymph node statuses, T-stage classifications, and treatment modalities., Methods: This is a population-based cohort study utilizing the Surveillance, Epidemiology, and End Results Program from 2004 to 2018. Propensity score-based inverse probability of treatment weighting was used to achieve covariate balance. Women with locally advanced cervical cancer on different lymph node statuses who underwent radical hysterectomy + pelvic lymphadenectomy + chemoradiotherapy, chemoradiotherapy, or radiotherapy alone were examined. Trends, patient characteristics, and survival outcomes were compared across different treatment regimens., Results: Among 8777 patients analyzed, patients with early T-stage and married were identified as independent protective factors for cancer-specific survival regardless of lymph node status. The survival outcomes ranked in descending order as follows: T1N0>T2N0>T1N1 = T2N1>T3N0>T3N1. Therefore, the FIGO Stage IIIC1 was re-stratified into IIC (T1N1+T2N1) and IIIC1(T3N1). Patients who underwent radical hysterectomy combined with adjuvant therapy exhibited superior 5-year cancer-specific survival rates compared to those treated with chemoradiotherapy among IB3, IIA2, and IIC. The therapeutic efficacy of chemoradiotherapy surpassed that of radiotherapy alone in IIIA, IIIB, IIIC1(T3N1), and IVA patients., Conclusion: Restratification of Stage IIIC1 based on T-stage effectively discerns patients with divergent prognoses. Radical surgery + chemoradiotherapy is significantly associated with improved survival in early T-stage, regardless of lymph node status in locally advanced cervical cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Oral and laryngeal squamous cell carcinoma (OSCC and LSCC) and papillary thyroid carcinoma (PTC) are common head and neck cancers (HNCs) typically treated surgically. Challenges in tumour delineation often lead to inadequate resection margins in OSCC and LSCC, and missed multifocality in PTC. Fluorescence imaging (FLI) using near-infrared tumour-targeting tracers may improve intraoperative identification of malignancy, facilitating precise excision. This study evaluates six potential FLI targets in OSCC, LSCC and PTC., Materials and Methods: Immunohistochemical staining was performed on OSCC (n = 20), LSCC (n = 10) and PTC (n = 10), assessing CEA, c-Met, EpCAM, EGFR, integrin αvβ6 and VEGF-α. Expression was scored (0-12) using the total immunostaining score (TIS) system, and categorized into absent (TIS 0), low (TIS 1-5), moderate (TIS 6-8) or high (TIS 9-12)., Results: Integrin αvβ6 showed significant overexpression in OSCC (TIS: 12; p < 0.001) and LSCC (TIS: 8; p = 0.002), with 80% of OSCC and 90% of LSCC exhibiting moderate-high expression. Similarly, EGFR expression was moderate-high in most OSCC (87.5%; TIS: 8) and universally high in LSCC (100%; TIS: 12). In PTC, EGFR and VEGF-α expressions were low-moderate, but significantly higher than in healthy tissue (TIS: 6; p < 0.006)., Conclusion: This study highlights integrin αvβ6 and EGFR as viable FLI targets in OSCC and LSCC, especially integrin αvβ6 for tumour margin delineation. In PTC, despite lower expressions, the significant overexpression of VEGF-α, c-MET, and EGFR suggests their potential as FLI targets. Our findings support the development of tumour-targeted FLI tracers to improve surgical precision in HNC., (© 2024. The Author(s).)

We used a mathematical approach to investigate the quantitative spatial profile of cancer cells and stroma in lung squamous cell carcinoma tissues and its clinical relevance. The study enrolled 132 patients with 3-5 cm peripheral lung squamous cell carcinoma, resected at the National Cancer Center Hospital East. We utilized machine learning to segment cancer cells and stroma on cytokeratin AE1/3 immunohistochemistry images. Subsequently, a spatial form of Shannon's entropy was employed to precisely quantify the spatial distribution of cancer cells and stroma. This quantification index was defined as the spatial tumor-stroma distribution index (STSDI). The patients were classified as STSDI-low and -high groups for clinicopathological comparison. The STSDI showed no significant association with baseline clinicopathological features, including sex, age, pathological stage, and lymphovascular invasion. However, the STSDI-low group had significantly shorter recurrence-free survival (5-years RFS: 49.5% vs. 76.2%, p < 0.001) and disease-specific survival (5-years DSS: 53.6% vs. 81.5%, p < 0.001) than the STSDI-high group. In contrast, the application of Shannon's entropy without spatial consideration showed no correlation with patient outcomes. Moreover, low STSDI was an independent unfavorable predictor of tumor recurrence and disease-specific death (RFS; HR = 2.668, p < 0.005; DSS; HR = 3.057, p < 0.005), alongside the pathological stage. Further analysis showed a correlation between low STSDI and destructive growth patterns of cancer cells within tumors, potentially explaining the aggressive nature of STSDI-low tumors. In this study, we presented a novel approach for histological analysis of cancer tissues that revealed the prognostic significance of spatial tumor-stroma distribution in lung squamous cell carcinoma., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Aims: The standard treatment of locally advanced cervical carcinoma is radical chemoradiation followed by brachytherapy which has improved survival. Hence, a major concern is our attempt to reduce the incidence of acute and late toxicities. IMRT has been shown to reduce toxicities. In this study, we have compared 3DCRT with IG-IMRT using patient-specific margins to evaluate tumor control as well as OAR-related toxicities., Materials and Methods: This was a single institution prospective phase III randomised control study including patients of squamous cell carcinoma of cervix (stage II-IIIB, FIGO 2009) without pelvic lymph node involvement. All patients were simulated using intermediate bladder filling protocol and those in the IG-IMRT arm, underwent additional scans with full and empty bladder to assess the range of internal motion and generate individualised ITV margin. EBRT dose of 46Gy/23#/4.5 weeks was delivered with weekly concurrent cisplatin followed by brachytherapy. All toxicities during EBRT and till 3 months post brachytherapy were considered acute toxicity. Post-treatment, patients were followed up every 2 months for first 2 years and then once every 6 months. Disease-related outcomes were assessed with clinical examination and symptom-directed imaging., Results: Two hundred patients were screened for inclusion and of them, 89 patients in 3DCRT and 84 patients in IG-IMRT arms were considered for final analysis. The baseline characteristics were comparable in both arms, majority of patients in both arms having stage II disease. For OARs, all dosimetric parameters were significantly better in the IG-IMRT arm. Acute radiation induced toxicities (dermatitis, genito-urinary and gastrointestinal toxicities) were significantly less in the IG-IMRT arm. The local, pelvic, and distant control were comparable in both arms., Conclusion: Based on our experience, the use of IG-IMRT with patient-specific ITV margins results in reduction in acute OAR toxicities in patients without compromising on tumor control., (Copyright © 2024 The Royal College of Radiologists. All rights reserved.)

Objectives: The M1/M2 macrophage framework is crucial in organ fibrosis and its progression to malignancy. This study investigated the possible role of M1/M2 macrophage interplay in the pathogenesis of oral submucous fibrosis (OSF) and its malignant transformation by analysing immunohistochemical expression of CD11c (M1) and CD163 (M2) markers., Methods: Immunohistochemistry was performed using primary antibodies against CD11c and CD163 on ten formalin-fixed paraffin-embedded tissue blocks for each group: (i) Stage 1 OSF, (ii) Stage 2 OSF, (iii) Stage 3 OSF, (iv) Stage 4 OSF, (v) well-differentiated squamous cell carcinoma (WDSCC) with OSF, and (vi) WDSCC without OSF. Ten cases of healthy buccal mucosa (NOM) served as controls., Results: Epithelial quick scores of M1 (CD11c) in NOM, Stages 1-4 OSF, and WDSCC with and without OSF were 0, 1.8, 2.9, 0.4, 0, 0, and 0, while connective tissue scores were 0, 3.2, 4.3, 2.7, 0.5, 1.2, and 2.4, respectively. Epithelial scores for M2 (CD163) were 0, 0.8, 0.8, 2.1, 0.6, 0.8, and 0.2, and connective tissue scores were 0, 1.8, 2.6, 3.9, 2.2, 5, and 4.4, respectively. Stages 3 and 4 OSF, WDSCC with and without OSF exhibited higher M2/M1 ratios compared to NOM and Stages 1-2 OSF., Conclusion: The interaction between M1 (CD11c) and M2 (CD163) macrophages, leading to M2 polarisation, plays a crucial role in the pathogenesis of OSF and its potential malignant transformation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Oral lichen planus (OLP) is a chronic inflammatory oral condition previously known to have a rate of malignant transformation of around 1%. Additionally, erosive lichen planus, a subtype of lichen planus, which is a known risk factor for malignant transformation, has previously been unquantified in a large cohort of patients. In a single unit observation between 2005 and 2021 we retrospectively assessed 1,920 patients who underwent histological analysis for suspected oral lichen planus, and followed the progression of their disease to assess the rate of malignant transformation. In total, 1.39% of OLP transformed to oral squamous cell carcinoma over an average of 5.8 years. However, we found that the transformation rate of erosive OLP into malignancy was 5.98% with an aggressive clinical pathway. To our knowledge the incidence of erosive OLP has not previously been quantified in a large cohort of patients. This retrospective study sheds light on, and raises warning signs about, the seriousness of this condition., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: Radiotherapy (RT) is an integral treatment part for patients with head and neck squamous cell carcinoma (HNSCC), but radioresistance remains a major issue. Here, we use MitoTam, a mitochondrially targeted analogue of tamoxifen, which we aim to stimulate ferroptotic cell death with, and sensitize radioresistant cells to RT., Materials and Methods: We assessed viability, reactive oxygen species (ROS) production, disruption of mitochondrial membrane potential, and lipid peroxidation in radiosensitive (UT-SCC-40) and radioresistant (UT-SCC-5) HNSCC cells following MitoTam treatment. To assess ferroptosis specificity, we used the ferroptosis inhibitor ferrostatin-1 (fer-1). Also, total antioxidant capacity and sensitivity to tert-butyl hydroperoxide were evaluated to assess ROS-responses. 53BP1 staining was used to assess radiosensitivity after MitoTam treatment., Results: Our data revealed increased ROS, cell death, disruption of mitochondrial membrane potential, and lipid peroxidation following MitoTam treatment in both cell lines. Adverse effects of MitoTam on cell death, membrane potential and lipid peroxidation were prevented by fer-1, indicating induction of ferroptosis. Radioresistant HNSCC cells were less sensitive to the effects of MitoTam due to intrinsic higher antioxidant capacity. MitoTam treatment prior to RT led to superadditive residual DNA damage expressed by 53BP1 foci compared to RT or MitoTam alone., Conclusion: MitoTam induced ferroptosis in HNSCC cells, which could be used to overcome the elevated antioxidant capacity of radioresistant cells and sensitize such cells to RT. Treatment with MitoTam followed by RT could therefore present a promising effective therapy of radioresistant cancers., Statement of Significance: Radiotherapy is applied in the treatment of a majority of cancer patients. Radioresistance due to elevated antioxidant levels can be overcome by promoting ferroptotic cell death combining ROS-inducing drug MitoTam with radiotherapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [J.N., J.S. and L.W. own part of MitoTam intellectual property]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Correlative imaging of cutaneous tumors provides additional information to the standard histopathologic examination. However, the joint progress in the establishment of analytical techniques, such as Laser-Induced Breakdown Spectroscopy (LIBS) and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) in clinical practice is still limited. Their combination provides complementary information as it is also shown in our study in terms of major biotic (Ca, Mg, and P) and trace (Cu and Zn) elements. To elucidate changes in the elemental composition in tumors, we have compiled a set of malignant tumors (Squamous Cell Carcinoma, Basal Cell Carcinoma, Malignant Melanoma, and Epithelioid Angiosarcoma), one benign tumor (Pigmented Nevus) and one healthy-skin sample. The data processing was based on a methodological pipeline involving binary image registration and affine transformation. Thus, our paper brings a feasibility study of a practical methodological concept that enables us to compare LIBS and LA-ICP-MS results despite the mutual spatial distortion of original elemental images. Moreover, we also show that LIBS could be a sufficient pre-screening method even for a larger number of samples according to the speed and reproducibility of the analyses. Whereas LA-ICP-MS could serve as a ground truth and reference technique for preselected samples., Competing Interests: Declaration of competing interest All authors hereby declare that they have no conflict of interest with regard to the presented study. Moreover, the ethical issues related to the handling and analysis of clinical samples (biopsies of human cutaneous tumors and healthy skin) were done under the approval of the ethical committee of the Hradec Králové University Hospital (ref. number 201805 S08P) where the patients were treated., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Berberine is an active compound found in different herbs used in Chinese medicine and is well-known for its potential anticancer properties. The study aimed to figure out the role of berberine in regulating the malignant behavior of laryngeal squamous cell carcinoma (LSCC) cells., Methods: LSCC cell lines (SNU-899 and AMC-HN-8) were treated with different concentrations of berberine (0-200 μM) to determine its cytotoxicity. The migration, invasion, and apoptosis of LSCC cells were measured by wound healing assays, Transwell assays, and flow cytometry. Western blot was performed for the quantification of proteins involved in PI3K/AKT/mTOR signaling., Results: The viability of LSCC cells was dose-dependently reduced by berberine. Berberine dampened LSCC cell migration and invasion while augmenting cell apoptosis, as evidenced by a reduced wound closure rate, a decrease in invaded cell number, and a surge in cell apoptosis in the context of berberine stimulation. Importantly, the effects of berberine on the cancer cell process were enhanced by LY294002 (an inhibitor for PI3K) treatment. Moreover, the protein levels of phosphorylated PI3K, AKT, and mTOR were markedly reduced in response to berberine treatment., Conclusion: Berberine inhibits cell viability, migration, and invasion but augments cell apoptosis by inactivating PI3K/AKT/mTOR signaling in LSCC., (©The Author(s) 2024. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Cutaneous squamous cell carcinoma (cSCC) arising from radiation dermatitis has a higher risk of metastasis than conventional cSCC. Immunosuppression is another risk factor for cSCC, suggesting that mycosis fungoides (MF) could be a risk factor for cSCC. Here we report a case of radiation-induced cSCC with a high level of tumor-mutation burden that developed in a patient with MF who was successfully treated with pembrolizumab. The present case suggests that pembrolizumab might be an optimal therapy for radiation-induced cSCC, even at advanced stages., (© 2024 Japanese Dermatological Association.)

Background: Despite trimodality treatment, 10% to 20% of patients with esophageal cancer experience interval metastases after surgery. Restaging may identify patients who should not proceed to surgery, as well as a subgroup with limited metastases for whom long-term disease-control can be obtained. This study aimed to determine the proportion of patients with interval metastases after neoadjuvant chemoradiotherapy (nCRT) and to evaluate treatment and survival., Methods: Patients who had cT2-4aN0-3M0 esophageal cancer treated with nCRT were identified from a trial database. Metastases detected up to 14 weeks after nCRT on 18 F-FDG-PET/CT or during surgery were categorized as oligometastases (≤3 lesions located in one single organ or one extra-regional lymph node station) or as non-oligometastases. The primary outcome was the proportion of patients with metastases after nCRT. The secondary outcomes were overall survival (OS) and the site and treatment of metastases., Results: Between 2013 and 2021, 973 patients received nCRT, and 10.3% had interval metastases. Of 100 patients, 30 (30%) had oligometastases, located mostly in non-regional lymph nodes (33.3%) or bones (26.7%). The median OS of this group was 13.8 months (95% confidence interval [CI] 9.2-27.1 months). Of 30 patients, 12 (40%) with oligometastases underwent potentially curative treatment, with a median OS of 22.8 months (95% CI 10.4-NA). The patients with non-oligometastases underwent mostly systemic therapy or BSC and had a median OS of 9 months (95% CI 7.4-10.9 months)., Conclusions: Interval metastases were detected in about 10% of patients after nCRT, underscoring the importance of re-staging with 18 F-FDG-PET/CT for those who proceed to surgery. A favorable survival might be accomplished for a subgroup of patients with oligometastases., (© 2024. The Author(s).)

Background: Although multiple treatment options exist for gastroesophageal junction (GEJ) cancer, surgery remains the mainstay for potential cure. Extended nodal dissection with a D2 lymphadenectomy (LAD) remains controversial for Siewert II GEJ cancer. Although D2 LAD may lead to a greater lymph node harvest, its effect on survival remains elusive. The authors hypothesized that additional D2 dissection in Siewert II GEJ cancer does not lead to increased survival., Methods: This study reviewed Siewert II patients who received a D1 or D2 LAD in addition to minimally invasive esophagectomy (MIE) after receiving neoadjuvant chemoradiation or perioperative chemotherapy (2012-2022). The patients were followed for up to 5 years. The outcomes measured were survival, number of nodes sampled, and operative time. The association between D1 or D2 LAD and overall survival was analyzed with Kaplan-Meier methods and a multivariable Cox regression model., Results: Among 155 patients, 74 % underwent D1 and 26 % underwent D2 LAD. The patients with D2 had more than 15 lymph nodes harvested more frequently than those who had D1 (83 % vs 48 %; p < 0.001), with no difference in positive nodes (2.8 ± 5.2 vs 2.1 ± 4.2; p = 0.4). The patients with D2 LAD had a longer median operative time than those who with D1 LAD (362 vs 244 min; p < 0.001). In Kaplan-Meier and multivariable Cox regression models, overall survival did not differ significantly between the patients undergoing D2 and those who had D1 (adjusted hazard ratio [aHR], 0.52; 95 % confidence interval [CI], 0.25-1.00; p = 0.067)., Conclusions: Little consensus exists regarding the optimal lymph node harvest for GEJ cancers. In Siewert II cancer, D2 LAD may not be mandatory and may lead to increased operative morbidity with no significant difference in survival., (© 2024. The Author(s).)

Pathological diagnosis plays a pivotal role in risk classification and personalized treatment planning for patients with oropharyngeal cancers. However, challenges arise in cases involving trismus and tumors with submucosal spread, hindering traditional endoscopic biopsies and open incisional biopsies. In this study, we examined the clinical and pathological data of patients with trismus who underwent transoral ultrasound-guided core biopsy (USCB) for their oropharyngeal tumors, comparing this method with existing diagnostic approaches. Seventeen patients presenting with oropharyngeal tumors and trismus underwent transoral USCB for diagnosis. Of these, 14 patients were diagnosed with squamous cell carcinoma, while the remaining 3 were diagnosed with lymphoma. The procedure resulted in minimal wound size and effective bleeding control through compression, without encountering any complications. In conclusion, transoral USCB emerges as a precise diagnostic tool for patients with oropharyngeal tumors and trismus, offering a valuable adjunct to conventional open and endoscopic biopsies., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Objectives: The aim of this study was to document 10-year outcomes after supracricoid partial laryngectomy (SCPL) in selected cT3M0 laryngeal squamous cell carcinoma (SCC) patients., Methods: This real-life retrospective observational study analyzed an inception cohort of 168 patients with isolated, untreated, selected cT3M0 laryngeal SCC, that were consecutively managed by SCPL during the period 1973-2013, and followed up until death or for a minimum of 10 years in 92% of cases at a single French academic and tertiary referral care center. Prior induction chemotherapy, arytenoid cartilage removal, level II-IV neck dissection, and postoperative radiation therapy were performed on 148, 77, 136, and 27 patients, respectively. The main objective was to determine 10-year actuarial local control and laryngeal preservation estimates. Secondary objectives included 10-year actuarial survival and cause-of-death analysis, and assessment of correlations between endpoints and clinical variables. The significance threshold was set at p < 0.005., Results: Ten-year actuarial local control, laryngeal preservation, and survival estimates were 90%, 85%, and 52%, respectively. Salvage treatment resulted in an overall 99% local control rate. Metachronous second primary cancer, intercurrent disease without evidence of SCC, SCPL-related death, and uncontrolled local recurrence accounted for 31%, 26%, 7%, and 2% of causes of death. On univariate analysis, overall local recurrence and laryngeal preservation rates varied significantly, from 5% to 54% and 90% to 46% when resection margins were R0 and R1, respectively., Conclusion: The present study highlighted successful 10-year outcomes after SCPL, providing further evidence in favor of its integration into the conservative armamentarium for endolaryngeal cT3 SCC., Level of Evidence: 4 Laryngoscope, 134:4557-4563, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Ear and temporal bone squamous cell carcinoma (ETBSCC) is a rare and aggressive malignant tumor with minimal clinicopathological studies. The object of this study was to retrospectively evaluate the predictive effect of clinicopathological variables on the 5-year overall survival (OS) rate of ETBSCC patients in a single tertiary medical center in Tianjin, China., Methods: A cohort of 44 patients with diagnosed ETBSCC from December 2012 to August 2022 were retrospectively studied. Univariate and multivariate analysis were, respectively, performed for the assessment of clinicopathological predictors, including sex, age, history of chronic suppurative otitis media (CSOM), lesion side, diameter, the choice of surgical approach, parotidectomy, neck dissection, adjuvant therapies, T stage, lymph node metastasis, tumor grade, margin, perineural invasion (PNI), and Ki-67 index., Results: Seventeen females and 27 males were included, with the mean age of 65 years old, ranging from 36 to 89 years. The 5-year OS rate was 43% (mean 51 months, 95% confidence interval [CI] = 39-64). Significant prediction of a worse prognosis for 5-year OS rate was observed under univariate analysis for advanced T stage, positive margin, identified PNI, and higher Ki-67 index, respectively. Advanced T stage was confirmed to be an independent prognostic factor strongly affecting 5-year OS rate among this cohort of patients using a multivariate cox proportional hazard model., Conclusion: We found that clinicopathological parameters, especially postoperative pathological parameters, play a critical role in predicting the prognosis of ETBSCC patients., (© 2024 Wiley Periodicals LLC.)

Background: High-risk cutaneous squamous cell carcinoma (cSCC) is associated with poor clinical outcomes. Traditionally, preoperative clinical tumor size ≥2 cm, based on Brigham and Women's Hospital (BWH) staging criteria, is high risk., Objective: To compare outcomes of cSCC treated with Mohs micrographic surgery (MMS) with a preoperative size ≥2 cm (clinically ≥2 cm) versus cSCC with preoperative size <2 cm and postoperative defect size ≥2 cm (histologically ≥2 cm)., Methods: Prospective data were collected from January 1, 2014, to December 31, 2020, on MMS cases for cSCC with a preoperative and/or postoperative size ≥2 cm. Clinical outcomes were followed until March 15, 2023. Data were analyzed using multivariate regression., Results: Three hundred thirty cases of MMS for cSCC were included. Cutaneous squamous cell carcinoma clinically ≥2 cm occurred more frequently in elderly patients; cSCC histologically ≥2 cm were more commonly located in the H region, required wider surgical margins, and more MMS stages to achieve clearance. There were no significant differences in rates of recurrence and metastasis between the groups., Conclusion: These data suggest that postoperative (histologic) MMS defect size may allow for better risk stratification of high-risk cSCC and improved staging of cSCC., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Aims: DEK::AFF2 squamous cell carcinoma is a recently described cancer entity, with 29 cases reported to date. Occasionally, these carcinomas appear deceptively indistinguishable; however, specific morphological and phenotypic features suggest the presence of this rearrangement. However, the prognostic value of this diagnosis remains unclear. We aimed to report a new case series with histological, molecular, and clinical features., Methods: We collected data from 15 patients and investigated their phenotypes, including the expression profiles of CK7, P63/P40, PDL1, AFF2, and P16, morphological features, and associated prognostic data. We analyzed these data along with the previously published data., Results: Most of these cases exhibited indicative morphological features, such as exophytic and endophytic papillary growth, nuclear monomorphism, and abundant neutrophil-rich inflammatory infiltrates. Immunohistochemical analysis revealed the expression of AFF2 and squamous cell markers in all the patients. Overexpression of P16 was not detected, whereas CK7 and PDL1 were expressed variably. In our study cohort, a 50% progression or recurrence rate, 25% lymph node metastasis, 17% distant metastasis, and 18% disease-related death were identified, with a short follow-up time., Conclusion: DEK::AFF2 squamous cell carcinoma incidence is probably underestimated. The low-grade appearance of these tumors sometimes limits their detection. The rates of recurrence and metastasis seem to be high despite an often bland morphology. We propose AFF2 immunohistochemistry as an effective tool, and a diagnostic algorithm has been established to support accurate diagnosis of these tumors., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Nasal vestibule squamous cell carcinoma (NVSCC) is an exceedingly rare malignancy, often misclassified due to its anatomical location and lack of a standardized definition. This review aims to consolidate current evidence on NVSCC, focusing on epidemiology, risk factors, classification, clinical presentation, treatment modalities, and prognostic factors. The NV anatomy is delineated, emphasizing the need for a clear definition to avoid misclassification. Risk factors include smoking, sunlight exposure, and debated associations with chalk exposure or viral factors. Clinical presentation includes symptoms like nasal obstruction, pain, burning, and bleeding, often misdiagnosed as inflammatory conditions. NVSCC exhibits distinct local spread patterns along cartilaginous surfaces, with the facial and submandibular lymph nodes at higher metastatic risk. Current classifications lack consensus, hindering comparison of outcomes. Treatment varies, with surgery or radiotherapy for early-stage tumors and multimodality approaches for advanced cases. The choice between surgery and radiotherapy is debated, with potential advantages and drawbacks for each. Radiotherapy, especially with Interventional RadioTherapy (IRT, previously known as brachytherapy), is gaining prominence, showing promising outcomes in terms of local control and cosmetic results. Prophylactic neck treatment remains controversial, with indications based on tumor characteristics. Prognostic factors include T classification, tumor size, surgical margins, nodal involvement, and histological features. Long-term survival rates range widely, emphasizing the need for further studies to refine management strategies for this rare malignancy. In conclusion, NVSCC poses diagnostic and therapeutic challenges, warranting multidisciplinary approaches and continued research efforts to optimize patient outcomes., (© 2024. The Author(s).)

Purpose: To explore the prevalence of synchronous and metachronous tonsillar cancer in patients with base of tongue cancer, as well as identifying potential risk factors linked to these secondary malignancies. We aim to answer the following question: Should bilateral tonsillectomy be recommended to patients diagnosed with base of tongue cancer?, Methods: A case-series study was conducted at Aarhus University Hospital, including all patients with histologically confirmed base of tongue squamous cell carcinoma treated between January 2012 and December 2021. Data from electronic patient records, including diagnosis of prior, synchronous or metachronous tonsillar cancer, demographics, and clinical features were analysed. Fisher's exact test was performed to assess factors associated with synchronous and metachronous tonsillar cancer., Results: Among 198 patients with base of tongue cancer, 5.6% had a history of tonsillar cancer, either prior to (4.5%), synchronous (0.5%), or metachronous (0.5%) to the base of tongue diagnosis. The prevalence of synchronous or metachronous tonsillar cancer among patients without previous bilateral tonsillectomy was 1.2%. Patients with tonsillar cancer were older, had heavier smoking histories, and exhibited less frequent P16-overexpression., Conclusion: Our findings deepen understanding of tonsillar cancer in patients with base of tongue cancer. The prevalence of synchronous or metachronous tonsillar cancer was found to be relatively low, suggesting that routine tonsillectomy for all base of tongue cancer patients is not warranted., (© 2024. The Author(s).)

Objectives: Laryngeal squamous cell carcinoma (SCC) is a predominantly male illness. Although the rate of female patients increased, a knowledge gap exists in the medical literature regarding gender-based differences., Design: Retrospective cohort study., Setting: Adult patients treated for laryngeal SCC in a tertiary medical centre between 2006 and 2020. Data were collected on demographics, clinical presentation, treatment modalities, disease recurrence and survival status., Participants: Two hundred ninety-one patients with laryngeal SCC, 50 (17.2%) females and 241 (82.8%) males., Main Outcome Measures: Disease-specific survival (DSS), overall survival (OS) and disease-free survival (DFS), as well as differences in disease characteristics and treatment modalities., Results: Tumour subsites differed significantly between females and males (36% vs. 19.5% supraglottic, 62% vs. 80.5% glottic and 2% vs. 0% subglottic, respectively; p = 0.006). Females were diagnosed at younger ages (61.7 ± 10.58 vs. 65.87 ± 11.11 years, p = 0.016) and advanced-stage disease (58% vs. 39.4%, p = 0.018). Females were treated with combined modalities at higher rates (36% vs. 54.8% for single modality, p = 0.031). DSS rates did not differ between genders (log-rank p = 0.12). Despite being diagnosed at more advanced disease stages, females demonstrated prolonged median OS compared to males (130.17 vs. 106.17 months, log-rank p = 0.017). No significant differences in DFS were observed (log-rank p = 0.32). In a multivariate Cox proportional hazards model, male gender remained an independent negative OS predictor (HR = 2.08; CI, 1.10-3.96; p = 0.025), along with increasing age (HR = 1.06; CI, 1.04-1.09; p < 0.001) and advanced disease stage (HR = 1.7; CI, 1.08-2.67; p = 0.023)., Conclusions: Our findings suggest the importance of considering gender-specific factors in the management of laryngeal SCC., (© 2024 The Author(s). Clinical Otolaryngology published by John Wiley & Sons Ltd.)

Oral squamous cell carcinoma (OSCC) is the most common oral malignancy. DEAD/H-box helicase 11 (DDX11), a DNA helicase, has been implicated in the progression of several cancers. Yet, the precise function of DDX11 in OSCC is poorly understood. The DDX11 expression in OSCC cells and normal oral keratinocytes was evaluated in the Gene Expression Omnibus database (GSE146483 and GSE31853). SCC-4 and CAL-27 cells expressing doxycycline-inducible DDX11 or DDX11 shRNA were generated by lentiviral infection. The role of DDX11 in OSCC cells was determined by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, colony formation assay, flow cytometry assay, TUNEL staining, and western blot. The effects of DDX11 on tumor growth were explored in a xenograft nude mouse model. The relationship between DDX11 and transcription factor Yin Yang-1 (YY1) was researched using the dual luciferase report assay and chromatin immunoprecipitation assay. DDX11 expression was significantly upregulated in OSCC cells. Knockdown of DDX11 inhibited cell proliferation, induced cell cycle arrest, and suppressed PI3K-AKT pathway, while DDX11 overexpression showed opposite effects. The number of apoptotic cells was increased in DDX11 silenced cells. DDX11 upregulation or knockdown accelerated or suppressed tumor growth in vivo, respectively. Moreover, the YY1 bound and activated the DDX11 promoter, resulting in increasing DDX11 expression. Forced expression DDX11 reversed the anticancer effects of YY1 silencing on OSCC cells. DDX11 has tumor-promoting function in OSCC and is transcriptionally regulated by YY1, indicating that DDX11 may serve as a potential target for the OSCC treatment., (© 2024 International Federation for Cell Biology.)

The aim of this study was to characterize the clinicopathological features and prognostic factors of T1/2 size (<4 cm) gingival squamous cell carcinoma (SCC) and to verify the impact of bone invasion. This was a single-centre, retrospective cohort study involving 206 patients with gingival SCC (maxilla or mandible), treated between 2000 and 2020. The patients were divided into three subgroups based on tumour size and bone invasion. The 5-year overall survival (OS) and disease-free survival (DFS) were 80.6% and 67.6%, respectively. Histological differentiation, advanced T stage, positive resection margin, bone invasion, and postoperative adjuvant therapy were associated with a poor prognosis (P < 0.05). Multivariate Cox analysis indicated that only histological differentiation (hazard ratio (HR) 2.68, P = 0.007) and bone invasion (HR 2.08, P = 0.036) were significantly associated with DFS. Bone invasion was observed in 145 (70.4%) patients, of whom 43 (20.9%) had a T1/2 size tumour. The subgroup with bone invasion and T1/2 size showed significantly worse OS and DFS when compared to the subgroup without bone invasion and similar or worse survival when compared to the subgroup with bone invasion and T3/T4 size. Histological differentiation and bone invasion were poor prognostic factors for gingival SCC, even in cases with small-sized tumours. For suspected bone invasion in small-sized tumours, an adequate bone margin is necessary and postoperative adjunctive therapy needs to be considered., (Copyright © 2024 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Poor differentiation predicts adverse outcomes in cutaneous squamous cell carcinoma (CSCC), but there is no standardized, reliable grading system., Objective: To explore which histologic features have the greatest impact on CSCC differentiation interrater agreement., Materials and Methods: In a prior study, 40 raters graded differentiation for 45 squamous cell carcinomas, and percent interrater agreements were calculated. Cases graded as well/moderately differentiated with 100% agreement (10), those graded as poorly differentiated with ≥80% agreement (5), and those that received a variety of grades with ≤60% agreement (7) were pulled for the current study. Three raters graded individual histologic features for each case, and percent interrater agreements were calculated using both the well/moderately/poorly differentiated grading system and a dichotomized system., Results: The percent interrater agreements were 34.8% for mitoses, 53% for pleomorphism, 59.1% for keratinization, 66.7% for cellular cohesion/intercellular bridges, and 78.8% for tumor edges. Percent agreements improved with dichotomous grading; the largest improvement was seen within the group of cases that had been graded as well/moderately differentiated with 100% agreement in the prior study., Conclusion: Future squamous cell carcinoma differentiation grading systems would benefit from eliminating mitotic rate, clearly defining how to grade other features, and dichotomous grading., (Copyright © 2024 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Nonmelanoma skin cancers (NMSC), comprising basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are typically encountered on photo-exposed skin. Nevertheless, several cases of NMSC have been described in covered areas such as the genital region; furthermore, some of these lesions may express a variable degree of pigmentation. Due to the existence of mucosal melanoma, an accurate diagnosis is paramount. In this narrative review, we focused our attention on management and - in particular- diagnosis of pigmented NMSC (pNMSC) located in the genital region, emphasizing the features assessed by dermoscopy and reflectance confocal microscopy. As an implementation, we included data on pNMSC from the Dermatology Unit of the University of Campania Vanvitelli. BCC in the genital region represents only 1% of all BCC cases. It has been supposed that the mutation of patched 1 may lead to the development of BCC even without concomitant UV exposure. Pigmented variants on genitals have seldom been described. More prominent dermoscopic features seem to be blue-gray ovoid nests and arborizing vessels associated with whitish structureless areas. SCC and Bowen's disease (BD) - a variant of in situ SCC - may be encountered in the genital area and are sometimes associated with human papillomavirus (HPV) infection. Pigmented SCC is very rare, and most of the literature is focused on pigmented BD (pBD), which is mainly characterized by gray-brown dots in a linear fashion and glomerular vessels without evident scales. In conclusion, pNMSC is rarely encountered on genitals; evaluation with dermoscopy or other ancillary devices like RCM is important both to exclude benign lesions like seborrheic keratosis and lentigo and to rule out melanoma., (© 2024 the International Society of Dermatology.)

Purpose: The influence of human immunodeficiency virus (HIV) infection on clinical outcomes in patients receiving (chemo)radiation therapy (RT) for squamous cell carcinoma of the anus (SCCA) is debated. The objective of this study was to compare efficacy and safety according to HIV status in patients with SCCA treated with C/RT., Methods and Materials: Between January 2015 and April 2020, 488 patients with a known HIV status (17.6% HIV+) were treated with radiation therapy for SCCA and included in the FFCD-ANABASE multicentric prospective cohort. Clinical outcomes including overall survival (OS), locoregional recurrence-free survival, colostomy-free survival, response rate at 4 to 6 months, cancer-specific survival, relapse-free survival, and severe acute and late toxicity were compared between HIV+ and HIV- patients., Results: The median follow-up was 35.8 months. HIV+ patients were younger (P < .01) and predominantly male (P < .01). Intensity modulated radiation therapy was performed in 80.7% of patients, and 80.9% received concurrent chemotherapy. A higher proportion of HIV+ patients received induction chemotherapy compared with HIV- patients. No statistically significant difference in overall treatment time or severe acute and late toxicities was found between HIV+ and HIV- patients. In univariate analyses, OS (HR = 2.1 [CI 95% 1.2;3.5], P = .007), locoregional recurrence-free survival (HR = 1.7 [1.1;2.7], P = .02), and colostomy-free survival (HR = 1.7 [1.1;2.6], P = .01) were significantly shorter in HIV+ patients than in HIV- patients. Response rate, cancer-specific survival, and relapse-free survival were not significantly different. The recurrence site was significantly different according to HIV status. In the multivariate analysis, prognostic factors for OS were a World Health Organization performance status of ≥1 for the whole population, as well as HIV+ status for the subgroup of women., Conclusions: HIV+ patients treated with chemo-RT for SCCA have poorer clinical outcomes, especially women. No difference was found in toxicity according to HIV status with intensity modulated radiation therapy technique., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Recurrent head and neck cancer presents a therapeutic challenge because of cumulative toxicity from initial radiation therapy, limiting reirradiation options. Boron neutron capture therapy (BNCT) offers a promising alternative, selectively delivering a radical dose to tumors while sparing adjacent normal tissue. This study investigates the initial clinical outcomes and prognostic factors associated with BNCT for recurrent squamous cell carcinoma of the head and neck., Methods and Materials: This retrospective analysis investigated the initial 47 patients treated with BNCT between May 2020 and February 2021 in Japan. All patients had received radiation therapy with a median dose of 70 Gy (range, 44-176) before BNCT. Median tumor size was 11 cm 3 (range, 1-117 cm 3 ), with 23% of tumors larger than 30 cm 3 , and 87% of patients had prior systemic therapy. The most common prescribed dose to the pharyngeal mucosa was 15 Gy-Eq (36%), followed by 18 Gy-Eq (34%). The minimum dose given to tumor was 27.4 Gy-Eq (range, 13.3-45.2). In 23 patients, 18 F-fluoro-borono-phenylalanine positron emission tomography was performed within 1 week before BNCT, and the tumor-to-blood 10 B ratio was 3.5 (range, 2.0-8.7)., Results: Efficacy analysis revealed a 51% complete response rate and a 74% overall response rate. Disease-free survival rates at 1 and 2 years were 34.6% and 26.6%, respectively. Overall survival rates at 1 and 2 years were 86.1% and 66.5%, respectively. Multivariate analysis revealed that, among the patient characteristics, whether the lesion was mucosal had a significant effect on achieving complete response., Conclusions: This study provided valuable insights into the early integration of BNCT into routine clinical practice, highlighting its efficacy and safety. Technical improvements are needed to ensure precise dose administration. Ongoing prospective studies, such as the phase II REBIVAL study, will further elucidate the role of BNCT in recurrent head and neck cancer., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Penile squamous cell carcinoma (PSCC) is classified into 2 prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. However, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with the prognosis of a large series of patients with PSCC. p53 was analyzed according to a recently described immunohistochemical (IHC) pattern-based framework that includes 2 normal and 4 abnormal patterns and closely correlates with TP53 mutational status. A total of 122 patients with surgically treated PSCC in 3 hospitals were included. Based on HPV in situ hybridization and p16 and p53 IHC, the tumors were classified into 3 subtypes: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed up for at least 22 months (median: 56.9 months). Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively ( P < 0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 abnormal patterns not recognized in the classic p53 IHC interpretation (basal, null, and cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired disease-specific survival (hazard ratio = 23.4, 95% CI = 2.7-3095.3; P = 0.001 and 16.3, 95% CI = 1.8-2151.5; P = 0.008, respectively). In conclusion, compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define 2 prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Hypopharyngeal cancer, constituting 3%-5% of head and neck cancers, predominantly presents as squamous cell carcinoma, with a 5-year overall survival rate of approximately 40%. Treatment modalities for locally advanced cases include chemoradiotherapy; however, the role of upfront neck dissection (UND) remains controversial. This study aimed to investigate the effect of UND on definitive radiotherapy in locally advanced hypopharyngeal carcinoma., Methods: This retrospective analysis included consecutive patients with locally advanced hypopharyngeal squamous cell carcinoma who were treated in our department between January 2007 and June 2023. All patients underwent definitive radiotherapy (dRT) at a total dose of 70 Gy in 35 fractions. The patients were categorized into two groups: dRT (radiotherapy with or without chemotherapy) and UND-dRT (surgical neck dissection followed by radiotherapy). Univariate Cox models and multivariate analyses were conducted to investigate the independent prognostic factors for overall survival and locoregional control rate., Results: This study included 115 patients, predominantly male (109/115), with a median age of 66 years. Clinical stage and chemotherapy distribution differed significantly between the dRT and UND-dRT groups. The 3-year overall survival and locoregional control rates for all patients were 63.8% and was 63.3%, respectively. The UND-dRT group exhibited a trend toward improved locoregional control, although this difference was not statistically significant. The multivariate analysis revealed that UND was an independent factor significantly associated with improved overall survival and locoregional control., Conclusion: This study provided evidence supporting the effectiveness of UND in conjunction with definitive radiotherapy for locally advanced hypopharyngeal carcinoma. Future research should focus on validating and refining these findings through well-designed prospective multicenter trials., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)