Oral Cavity Squamous Cell Carcinoma Research Articles

Acute NMOSD Attack in the Setting of Pembrolizumab Therapy: A Case Report (P13-5.009)

Acute NMOSD Attack in the Setting of Pembrolizumab Therapy: A Case Report (P13-5.009)

Prognostic impact of the hemoglobin–albumin–lymphocyte–platelet score in patients with oral cavity cancer undergoing surgery

We aimed to probe the hemoglobin-albumin-lymphocyte-platelet (HALP) score's prognostic value in oral cavity squamous cell carcinoma (OSCC). Medical data of 350 patients with primary operated OSCC were retrospectively reviewed. We derived the optimal HALP cutoff by executing receiver operating characteristic curve analysis, and patients were then grouped based on this cutoff value. Cox proportional hazards model were used to discover survival outcome-associated factors. We derived the optimal HALP cutoff as 35.4. A low HALP score (<35.4) predicted poorer overall and disease-free survival (hazard ratio: 2.29 and 1.92, respectively; both p < 0.001) and was significantly associated with OSCC aggressiveness. We established a HALP-based nomogram that accurately predicted overall survival (concordance index: 0.784). The HALP score may be a useful prognostic biomarker in patients with OSCC undergoing surgery, and the HALP-based nomogram can be a promising prognostic tool in clinical setting.

Marginal versus Segmental Mandibulectomy in the Treatment of Oral Cavity Cancer: A Systematic Review and Meta-analysis.

Introduction Oral cavity squamous cell carcinoma (OCSCC) is the most common malignancy in the oral cavity. Two types of mandibular resections have been described: the segmental mandibulectomy and the marginal mandibulectomy. Both may have a different impact over the quality of life, oncological prognosis, and functional or aesthetic result. Objectives The aim of this study was to systematically explore the literature to determine the survival outcomes and disease control rates in patients who underwent segmental or marginal mandibulectomy for OCSCC with histological evidence of cortical and medullary bone invasion. Data Synthesis This review involved a systematic search of the electronic databases MEDLINE/PUBMED, Google Scholar, Ovid Medline, Embase, and Scopus including articles from 1985 to 2019. Fifteen articles were included for qualitative analysis and 11 articles were considered for meta-analysis calculations. All of them correspond to retrospective cohort studies. Conclusion This systematic review reveals the low-level evidence regarding the impact over local control or survival according to the type of mandibulectomy. Our results need to be considered with precaution according to the limited evidence available. We just found difference regarding the 5-year disease-free survival, and a tendency in favor of segmental mandibulectomy was confirmed when medullary invasion was evident.

Oral Cavity Squamous Cell Carcinoma: An Update of the Pharmacological Treatment

Oral cavity squamous cell carcinoma (OCSCC) represents a serious health and socio-economic problem in different geographical areas of the world. It is characterized by a high rate of mortality, recurrence and metastasis. Despite the therapeutic strategies implemented for its management and resolution, currently the survival estimate for locally advanced disease is about 50%. The available therapeutic options comprise surgery and pharmacological treatment. Recently, an increased emphasis has been placed on the drugs that might be of benefit in this life-threatening disease. Therefore, the aim of this present review was to offer a general survey of the current available pharmacological treatment for OCSCC. The PubMed database was used to retrieve the papers using "OCSCC" as the search terms. We limited our search to the last 5 years to give a more updated and recent picture of the state of the art, including preclinical and clinical investigations. We found that 77 out of 201 papers were on the surgical treatment of OCSCC, 43 out of 201 focused on the radiotherapy and 81 out of 201 underwent evaluation for the aim of our review. We excluded the case reports, editorial letters, observational studies and papers written in languages other than English. A total of 12 articles were included in the final review. Our results showed that nanotechnologies use to enhance the efficacy of anticancer drugs such as: cisplatin, paclitaxel, cetuximab, EGFR antagonists, MEK1/2 and immune check inhibitors combination could have promising anti-cancer activity. However, the paucity of available data on drugs suggests the urgent need to improve the pharmacological armamentarium for OCSCC treatment.

Abstract 5986: The CDK4/6 inhibitor palbociclib sensitizes oral cavity squamous cell carcinoma to navitoclax-induced apoptosis-An in vitro and in vivo study

Abstract INTRODUCTION: CDKN2A, coding for p16INK4a, a CDK4/6 inhibitory protein, is among the most commonly lost tumor suppressors in oral cavity squamous cell carcinoma (OCSCC). Drugs like palbociclib are CDK4/6 inhibitors that phenomenally also induce senescence. Senescence can be pro-tumorigenic. Studies suggests prosurvival BCL-2 family support tumor cell survival in senescent state. Agents targeting BCL-2 family e.g. navitoclax, are “senolytics” The current study examines combining palbociclib (P) with the senolytic agent navitoclax (N) as a treatment strategy. We demonstrate efficacy of combining P+N in OCSCC, and examine senescence and apoptosis processes as related mechanistic response of combination. EXPERIMENTAL PROCEDURE: We examined cell viability after sequential treatment: 72 h P followed by 72 h N (P+N) in 2-dimensional (2D) model of immortalized cell line HN5 and 3D model of a human OCSCC patient-derived conditional reprogrammed cell line (CR18). Flow cytometry measured apoptosis with Annexin V assay in 2D. Confocal imaging in 3D spheroids corroborated pro-survival protein levels. An in vivo xenograft study was performed with HN5 in 8 weeks old male nude mice to examine tumor responses to sequential P+N treatment. 3 million cells were injected in right flank. Tumors were treated at ~300 mm3 (P-100 mg/kg o.p; N -17 mg/kg i.p). After treatment termination, Bcl-2 family proteins (BcLxl); apoptosis markers (caspase 3, Cleaved PARP) and β-galactosidase (β -gal) for senescence were evaluated with western blot. QPCR measured expression of CDK4/6 target (FOXM1) to examine senescence and pro survival genes. RESULTS: Sequential treatment of P+N (1µM each) demonstrated consistent synergy in both 2D and 3D viability assays. Bright field images of P+N revealed senescence with P followed with apoptosis on N application. β -gal levels increased to 1.5 fold with P and Caspase 3 showed 2-fold increase with P+N. Flow cytometry data revealed 2 folds increase in the apoptotic population with P+N. Confocal imaging in organoids demonstrated increased levels of BcLxL with P, and repression of BCL-xL following N administration. Sequential P+N significantly reduced tumor growth in vivo. P+N demonstrated a robust 5-fold decrease in tumor volume (TV) with a complete cure (TV&amp;lt;20 mm3) in 60% population in comparison to either of the cohorts post 30 days of treatment (control: 2000 mm3, P- 1200 mm3; N- 1500 mm3, p&amp;lt;0.05). Compared to control sequential P+N treatment in vivo i) reduced anti-apoptotic BcLxL mRNA expression to 2.5 fold ii) Cleaved PARP increased 10 folds and iii) BcLxL levels decreased 2 fold. CONCLUSION: Our results suggest that CDK4/6 inhibition makes OCSCC undergo senescence and make it more susceptible to apoptosis when combined with the BCL2-family inhibitor, navitoclax. We propose a sequential P+N as a rational and potentially effective treatment strategy in OCSCC. Citation Format: Nitisha Shrivastava, Nicole Kawachi, Michael B. Prystowsky, Evripidis Gavathiotis, Chandan Guha, Thomas J. Ow. The CDK4/6 inhibitor palbociclib sensitizes oral cavity squamous cell carcinoma to navitoclax-induced apoptosis-An in vitro and in vivo study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5986.

Abstract 2103: Immunophenotyping of extracellular vesicles isolated from lymphatic exudate identifies CD24 as a marker for lymph node metastases in oral cavity squamous cell carcinoma

Abstract Background: Squamous cell carcinoma of the oral cavity (OSCC) is debilitating and fatal with a high risk of lymph node metastases. One of the key problems is that currently there is no robust molecular biomarker to determine whether the tumor has spread or is at risk of spreading to the regional lymph nodes, the first echelon that OSCC spreads to. Extracellular vesicles (EVs) are functional nanoparticles that are bound by natural protein-lipid bilayers. They are deliberately packaged and proactively secreted by all types of cells and serve as intercellular communication vehicles. Tumors release an excess of EVs which are loaded with the molecular and genetic cargo of the parental tumor cells. Methods: Following ethical approval and written informed consent, pre-surgical plasma as well as matched post-surgical lymphatic drainage fluid were collected from 20 OSCC patients (nodal disease n=6, no node n=14), and control plasma was also collected from healthy donors. EVs were isolated by ultracentrifugation, quantified and characterized by nanoparticle tracking analysis, transmission electron microscopy, and western blot. Immune profiling of 37 EV surface markers was determined using flow cytometry with the MACSPlex Exosome kit. Results: Lymphatic exudate was greatly enriched in EVs in comparison to plasma. Common EV tetraspanins, platelet markers, cancer-related proteins, as well as characteristic markers of immune cells were detected in both plasma and lymphatic exudate EVs based on normalized median fluorescence intensity (nMFI). The presence of OSCC led to an altered composition of blood cell-derived EVs. Elevated levels of CD3, CD25, and CD86, and cancer stem cell marker CD133 were observed in the plasma EVs. However, there were no significant changes in EV markers in plasma between patients with and without lymph node metastasis. Notably, EVs isolated from plasma and lymphatic exudate revealed completely divergent signatures of EV surface markers. Among them, cancer-related protein CD24 was found to be the most highly expressed EV marker in lymphatic exudate from patients with nodal disease (nMFI 1.28±0.50 versus 0.84±0.32, p&amp;lt;0.05) and likewise correlated with advanced disease stages (nMFI 1.17±0.40 versus 0.70±0.27, p&amp;lt;0.05). Conclusions: Plasma-derived EVs are promising non-invasive biomarkers for cancer detection. This study shows that lymphatic exudate is a better source of EV biomarkers due to its high abundance of tumor-related factors directly from draining lymph nodes. In addition, CD24, as reported, is indicative of an immunosuppressive tumor microenvironment and it may serve as a predictor for lymph node metastases and progression of OSCC. These findings shed new light on the understanding of OSCC metastases and provide impetus for consideration of CD24-based liquid biopsy testing and possibly novel immunotherapy. Citation Format: Xinyu Qu, Leanne Lee Leung, Cherrie Wing Kei Ng, Hiu Ching Chan, Zigui Chen, Katie Meehan, Xianhai Zeng, Jason Ying Kuen Chan. Immunophenotyping of extracellular vesicles isolated from lymphatic exudate identifies CD24 as a marker for lymph node metastases in oral cavity squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2103.

Prognostic Significance of Worst Pattern of Invasion in oral cavity Squamous Cell Carcinoma in relation to lymph node metastasis —A Retrospective Study from tertiary care centre

Prognostic Significance of Worst Pattern of Invasion in oral cavity Squamous Cell Carcinoma in relation to lymph node metastasis —A Retrospective Study from tertiary care centre

Abstract 4845: Ultra-deep sequencing of mitochondrial genome to explore the dynamic mutational changes associated with oral cavity squamous cell carcinoma progression

Abstract Oral cavity squamous cell carcinoma (OCSCC) is a devastating disease, causing substantial morbidity and mortality. While many OCSCCs arise from an existing dysplastic lesion, not all oral premalignant lesions progress to OCSCC. Current methods for oral premalignancy and OCSCC diagnosis (visual and tactile exam followed by tissue biopsy and histologic evaluation) cannot discriminate between benign inflammatory changes and high-risk premalignant lesions that require interventions, underscoring the need for molecular-based biomarkers. The multi-step cancer progression from normal epithelium to premalignant lesion and invasive SCC is driven by the accumulation of genetic alterations, including changes in mitochondrial DNA (mtDNA). Due to the lack of protective histones and limited repair mechanisms, mtDNA is susceptible to damage by environmental carcinogens and reactive oxygen species, a byproduct of the oxidative phosphorylation system. As a result, mutation rate in mtDNA is ~10 times higher than in nuclear DNA, and may greatly facilitate the risk of mitochondrial dysfunction. Previous studies underscore that acquisition of somatic mtDNA mutations directly involved in tumorigenesis, and not merely epiphenomena. However, the impact of these studies is limited by an incomplete understanding of mitochondrial genomic alterations in the transition of preneoplastic lesions to invasive disease. In this study we used a unique cohort of 27 patients with matched longitudinally collected samples (histologically normal mucosa, dysplastic lesion, and SCC) coupled with novel ultra-deep mitochondrial sequencing (mtDNA-Seq) method to assess the mtDNA mutational landscape throughout the continuum of OCSCC progression. Using a custom bioinformatics workflow, somatic mutations were detected in a subset of the premalignant lesions, with overall higher mutational load observed in OCSCC specimens. While sequencing revealed a large degree of inter-patient heterogeneity, a panel of non-synonymous aberrations were present in both premalignant and invasive neoplasms. The majority of shared mutations showed an increase in fractional abundance in tumors, compared to the precursor lesions (suggesting a spatial expansion of these clones as they progressed histologically), and were enriched for coding mutations in complex-I subunits (critical region for ATP production), which is associated with an oncogenic phenotype. Additionally, mtDNA content increased in OCSCC tumor in a subset of patients, suggesting a cell compensation for defective oxidative phosphorylation and lower ATP production per mitochondria. Here we report the first comprehensive characterization of mitochondrial mutational landscape in dysplastic and invasive SCC lesions, and reveal key molecular events associated with the transition from non-invasive to invasive state. Citation Format: Alka Singh, Ashwin Lakshman Koppayi, Ping Wu, Mark Lingen, Vasudha Mishra, Alexander Pearson, Ari Rosenberg, Nishant Agrawal, Karthik Suresh, Evgeny Izumchenko. Ultra-deep sequencing of mitochondrial genome to explore the dynamic mutational changes associated with oral cavity squamous cell carcinoma progression. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4845.

Does lymphovascular invasion predict survival in oral cancer? A population-based analysis

ObjectiveTo evaluate lymphovascular invasion as an independent predictor for overall survival in patients with oral cavity squamous cell carcinoma. Study DesignRetrospective cohort study. SettingMulti-center, population-based facilities reporting to the National Cancer Database registry. MethodsThe database was accessed to collect data on patients with oral cavity squamous cell carcinoma. A multivariate cox proportional hazards model was used to analyze the association between presence of lymphovascular invasion and overall survival. Results16,992 patients met inclusion criteria. 3,457 patients had lymphovascular invasion. The mean follow-up was 32 ± 19 months. Lymphovascular invasion predicted reduced 2-year overall survival (relative hazard 1.29, 95% CI: 1.20, 1.38, p < 0.001) and 5-year overall survival (relative hazard 1.30, 95% CI: 1.23, 1.39, p < 0.001). LVI reduced overall survival in patients with squamous cell carcinoma of the oral tongue (HR: 1.27, 95% CI: 1.17, 1.39, p < 0.001), floor of mouth (HR: 1.33, 95% CI: 1.17, 1.52, p < 0.001) and buccal mucosa (HR: 1.44, 95% CI: 1.15, 1.81, p = 0.001). Patients with lymphovascular invasion treated with surgery plus post-operative radiotherapy had significantly improved survival compared to those who underwent surgery alone (relative hazard 1.79, 95% CI: 1.58, 2.03, p < 0.001), and patients treated with surgery + post-operative chemoradiotherapy had improved survival compared to those treated with surgery alone (relative hazard 2.0, 95% CI: 2.26, 1.79, p < 0.001). ConclusionLymphovascular invasion is an important independent risk factor for decreased overall survival in oral cavity squamous cell carcinoma involving the oral tongue, floor of mouth and buccal mucosa subsites.

A state-of-the-art approach for dental diagnosis using machine learning assessment

In the modern era, intelligent systems are playing a vital role in day-to-day human life-related applications. It is not only giving solutions to handling health-care applications for dental treatments. In this context, artificial intelligence-based machine learning (ML) algorithms are used for experimenting with the trained data sets that progress the relevances in decision-making. A specific practice The “Internet of Dental Things” is a ground-breaking method to accomplish the avoidance and supervision of periodontal diseases, dental caries, oral cancers, and other dental diseases. Various ML algorithms such as convolutional neural network, K-nearest neighbor, and random Forest are used for anticipating nodal status and tumor grade in oropharyngeal and oral cavity squamous cell carcinoma. The ML algorithms help with diagnosis, assistive systems, and monitoring toward decision-making and contribute to the pursuit of suggesting an exact dental treatment. It is helpful in diagnosing tooth loss, cracked teeth, periodontitis, dental fluorosis, dental caries, dental calculus, dental plaque, and periodontal disease. The suggestions given by the intelligent system render accuracy, precision, specificity, sensitivity, confusion matrix, recall, and F1-Score to strengthen the decision-making and contribute to the pursuit of offering an exact treatment.

Predictors of recurrence in oral cavity cancer with clear surgical margins

Introduction: Oral cancers recur in a significant proportion of patients, in spite of aggressive treatment strategies. The presence of a clear surgical margin is an important predictor of recurrent disease, among others. Since oral cancers often recur in the absence of compromised margins, there is a need to study the factors affecting recurrence and overall survival outcomes where clear surgical margins have been achieved during upfront surgery. This study attempts to identify the significant predictors of locoregional recurrence in oral squamous cell carcinoma (OSCC) with pathologically clear surgical margins. Methodology: This retrospective study was done to study the clinicopathological parameters associated with recurrence of oral cavity squamous cell carcinoma (SCC) in patients with clear surgical margins operated in our unit between January 2010 and December 2015. A total of 526 cases of oral cavity SCC were analyzed and records of 160 cases with clear surgical margins were reviewed for clinical details, histopathological data, and follow-up status. Age, gender, subsite, T–N clinical and pathological staging, tumor depth of invasion, grade of differentiation, lymphovascular invasion, perineural spread, adjuvant therapy, and recurrence details were analyzed. Results: Lymphovascular Invasion was found to be a significant predictor for local recurrence in OSCC in both univariate and multivariate analysis. Median recurrence-free survival was 53.6 months. Conclusion: Despite the best efforts of the surgeon in obtaining adequate tumor-free margins and the most comprehensive adjuvant treatment, recurrence patterns in oral cancers continue to defy accurate prediction. Lymphovascular invasion could be an important predictor of recurrence for oral cavity cancers in patients with clear surgical margins that require aggressive management.

CDK4/6 Inhibition Induces Senescence and Enhances Radiation Response by Disabling DNA Damage Repair in Oral Cavity Squamous Cell Carcinoma.

HPV(-) OCSCC resists radiation treatment. The CDKN2A gene, encoding p16INK4A, is commonly disrupted in OCSCC. p16 inhibits CDK4/CDK6, leading to cell cycle arrest, but the biological sequelae of CDK4/6 inhibition in OCSCC remains understudied. This study examines whether inhibition of CDK4/6 enhances radiation response in OCSCC. MTT assays were performed in OCSCC cell lines HN5 and CAL27 following treatment with palbociclib. Clonogenic survival and synergy were analyzed after radiation (RT-2 or 4Gy), palbociclib (P) (0.5 µM or 1 µM), or concurrent combination treatment (P+RT). DNA damage/repair and senescence were examined. CDK4/6 were targeted via siRNA to corroborate P+RT effects. Three-dimensional immortalized spheroids and organoids derived from patient tumors (conditionally reprogrammed OCSCC CR-06 and CR-18) were established to further examine and validate responses to P+RT. P+RT demonstrated reduced viability and synergy, increased β-gal expression (~95%), and ~two-fold higher γH2AX. Rad51 and Ku80 were reduced after P+RT, indicating impairment of both HR and NHEJ. siCDK4/6 increased senescence with radiation. Spheroids showed reduced proliferation and size with P+RT. CR-06 and CR-18 further demonstrated three-fold reduced proliferation and organoids size with P+RT. Targeting CDK4/6 can lead to improved efficacy when combined with radiation in OCSCC by inducing senescence and inhibiting DNA damage repair.

Indications for elective neck dissection in cT1N0M0 oral cavity cancer according to the AJCC eight edition: A nationwide study

ObjectivesAccording to the NCCN guidelines, there is weak evidence to support the use of elective neck dissection (END) in early-stage oral cavity squamous cell carcinoma (OCSCC). We sought to examine the indications for END in patients with cT1N0M0 OCSCC defined according to the AJCC Staging Manual, Eight Edition. MethodsOf the 3886 patients diagnosed with cT1N0M0 included in the study, 2065 underwent END and 1821 neck observation. ResultsThe 5-year outcomes for patients who received END versus neck observation before and after propensity score matching (n = 1406 each) were as follows: neck control, 96 %/90 % (before matching), p < 0.0001; 96 %/90 % (after matching), p < 0.0001; disease-specific survival (DSS), 93 %/92 % (before matching), p = 0.0227; 93 %/92 % (after matching), p = 0.1436. Multivariable analyses revealed that neck observation, depth of invasion (DOI) > 2.5 mm, and poor differentiation were independent risk factors for 5-year outcomes. Upon the application of a scoring system ranging from 0 (no risk factor) to 3 (presence of the three risk factors), the following 5-year rates were observed: neck control, 98 %/95 %/84 %/85 %; DSS, 96 %/93 %/88 %/85 %; and overall survival, 90 %/86 %/79 %/59 %, respectively (all p < 0.0001). The survival outcomes of patients with scores of 0 and 1 were similar. The occult metastasis rates in the entire study cohort, DOI > 2.5 mm, and poor differentiation were 6.8 %/9.2 %/17.1 %, respectively. ConclusionBecause all patients who received neck observation had a score of 1 or higher, END should be performed when a DOI > 2.5 mm or poorly differentiated tumors are present. Under these circumstances, 48.6 % (1888/3886) of cT1N0M0 patients may avoid END without compromising oncological outcomes.

Cover Image, Volume 62, Issue 4

The cover image is based on the Research Article Plasma cell-free DNA methylome profiling in pre- and postsurgery oral cavity squamous cell carcinoma by Krupal B. Patel et al., https://doi.org/10.1002/mc.23501.

A nationwide study on cancer recurrences, second primary tumours, distant metastases and survival after treatment for primary head and neck cancer in the Netherlands

IntroductionThere is no consensus on the optimal duration of post-treatment follow-up after head and neck cancer (HNC). To generate site-specific input for follow-up guidelines, this study describes the incidence and timing of manifestations of disease during five years of follow-up. MethodsAll patients diagnosed with HNC in the Netherlands in 2015 were selected from the Netherlands Cancer Registry. The follow-up events local recurrence (LR), regional recurrence (RR), second primary tumour (SPT), distant metastasis (DM) and death were studied per follow-up-year. The cumulative incidence of these events was calculated using competing risk analyses, with LR, RR and SPT of the head and neck (SPHNC) as events and SPT outside the head-neck (SPOHN), DM and death as competing events. Analyses were performed for oral cavity-, oropharynx-, larynx- and hypopharynx squamous cell carcinoma (SCC), and all HNC patients. ResultsThe 1-, 1.5-, and 2-year cumulative incidence of an event (LR, RR, SPHNC) were 10% (95%CI 8–13), 12% (95%CI 10–15), and 13% (95%CI 10–16) for oral cavity SCC; 6% (95%CI 4–9), 10% (95%CI 7–14), and 11% (95%CI 8–15) for oropharynx SCC; 7% (95%CI 5–10), 11% (95%CI 9–15), and 13% (95%CI 10–16) for larynx SCC and 11% (95%CI 6–19), 19% (95%CI 12–27), and 19% (95%CI 12–27) for hypopharynx SCC. ConclusionsOne year of follow-up for oral cavity SCC, and 1.5 years for oropharynx-, larynx-, and hypopharynx SCC suffices for the goal of detecting disease manifestations after treatment. More research into other aspects of follow-up care should be performed to determine the optimal follow-up regimen.

Prophylactic versus reactive feeding approach in patients undergoing adjuvant radiation therapy for oral cavity squamous cell carcinoma: A propensity score matched-pair analysis.

To assess the efficacy of prophylactic versus reactive feeding strategy in oral cavity squamous cell carcinoma (OCSCC) patients receiving adjuvant radiation therapy (RT). This was a post hoc analysis of patients of OCSCC enrolled in a randomized trial comparing three adjuvant strategies. In this trial, till 2010, a prophylactic feeding approach was followed for all patients. Since January 2011, a reactive feeding approach was followed. Two hundred and sixty-eight in each cohort (total n= 526) were eligible for analysis after propensity score matching. At 6 weeks post-RT completion, the median weight loss in the prophylactic versus reactive cohort was 5 versus 3 kg, p= 0.002. At all other time points until 1 year, the median weight loss was lesser in reactive than in the prophylactic cohort. A reactive feeding tube approach should be preferred for OCSCC receiving adjuvant RT.

Predictors of survival in advanced oral cancers after salvage surgery with free tissue flap reconstruction

ObjectiveTo identify prognostic factors for patients with advanced persistent, recurrent, or 2nd primary oral cavity squamous cell carcinoma (OCSCC) potentially unsuitable for salvage surgery with free tissue flap (FTF) reconstruction.Materials and methodsA population-based cohort of 83 consecutive patients with advanced OCSCC who underwent salvage surgery with FTF reconstruction at a tertiary referral centre between 1990 and 2017. Retrospective uni- and multivariable analyses were performed to identify factors affecting all-cause mortality (ACM), i.e., overall survival (OS), as well as disease-specific mortality (DSM), i.e., disease-specific survival (DSS) after salvage surgery.ResultsMedian disease-free interval until recurrence was 15 months with recurrent stage I/II in 31% and III/IV in 69%. Median age at salvage surgery was 67 years (range 31–87) and the median follow-up (alive patients) 126 months. At 2, 5, and 10 years after salvage surgery, respectively, DSS rates were 61%, 44%, and 37% and OS rates 52%, 30%, and 22%. Median DSS was 26 and OS 43 months. Multivariable analysis identified recurrent clinical regional (cN-plus) disease [HR 3.57; p < .001] and elevated gamma-glutamyl transferase (GGT) [HR 3.30; p = .003] as independent pre-salvage predictors for poor OS after salvage, whereas initial cN-plus [HR 2.07; p = .039] and recurrent cN-plus disease [HR 5.14; p < .001] predicted poor DSS. Among post-salvage factors, extranodal extension according to histopathology [HR ACM 6.11; HR DSM 9.99; p < .001] as well as positive [HR ACM 4.98; DSM 7.51; p < 0.001] and narrow surgical margins [HR ACM 2.12; DSM HR 2.80; p < 0.01] emerged as independent factors for poor survival.ConclusionWhile salvage surgery with FTF reconstruction is the primary curative option for patients with advanced recurrent OCSCC, the present findings may help guide discussions with patients who have advanced recurrent regional disease and high GGT preoperatively, especially if there is a small chance of reaching surgical radicality.

Convergent dysbiosis of upper aerodigestive microbiota between patients with esophageal and oral cavity squamous cell carcinoma.

The bidirectional association between primary esophageal squamous cell carcinoma (ESCC) and oral cavity squamous cell carcinoma (OSCC) suggests common risk factors and oncogenic molecular processes but it is unclear whether these two cancers display similar patterns of dysbiosis in their upper aerodigestive microbiota (UADM). We conducted a case-control study to characterize the microbial communities in esophageal lavage samples from 49 ESCC patients and oral rinse samples from 91 OSCC patients using 16S rRNA V3-V4 amplicon sequencing. Compared with their respective non-SCC controls from the same anatomical sites, 32 and 45 discriminative bacterial genera were detected in ESCC and OSCC patients, respectively. Interestingly, 20 of them were commonly enriched or depleted in both types of cancer, suggesting a convergent niche adaptation of upper aerodigestive SCC-associated bacteria that may play important roles in the pathogenesis of malignancies. Notably, Fusobacterium, Selenomonas, Peptoanaerobacter and Peptostreptococcus were enriched in both ESCC and OSCC, whereas Streptococcus and Granulicatelia were commonly depleted. We further identified Fusobacterium nucleatum as the most abundant species enriched in the upper aerodigestive SCC microenvironment, and the higher relative abundances of Selenomonas danae and Treponema maroon were positively correlated with smoking. In addition, predicted functional analysis revealed several depleted (eg, lipoic acid and pyruvate metabolism) and enriched (eg, RNA polymerase and nucleotide excision repair) pathways common to both cancers. Our findings reveal a convergent dysbiosis in the UADM between patients with ESCC and OSCC, suggesting a shared niche adaptation of host-microbiota interactions in the pathogenesis of upper aerodigestive tract malignancies.

Early relapse is an adverse prognostic factor for survival outcomes in patients with oral cavity squamous cell carcinoma: results from a nationwide registry study

BackgroundThe prognostic significance of the relapse interval in patients with resected oral cavity squamous cell carcinoma (OCSCC) is a matter of ongoing debate. In this large-scale, registry-based, nationwide study, we examined whether the time interval between surgery and the first disease relapse may affect survival outcomes in Taiwanese patients with OCSCC.MethodsData made available by the Taiwan Health Promotion Administration as of 2004 were obtained. The study cohort consisted of patients who were included in the registry between 2011 and 2017. Disease staging was performed according to the American Joint Committee on Cancer (AJCC) Staging Manual, Eight Edition. We retrospectively reviewed the clinical records of 13,789 patients with OCSCC who received surgical treatment. A total of 2327 (16.9%) patients experienced a first disease relapse. The optimal cutoff value for the relapse interval was 330 days when both 5-year disease-specific survival (DSS) and overall survival (OS) (≤ 330/>330 days, n = 1630/697) were taken into account. In addition, we undertook a propensity score (PS)-matched analysis of patients (n = 654 each) with early (≤ 330 days) versus late (> 330 days) relapse.ResultsThe median follow-up time in the entire study cohort was 702 days (433 and 2001 days in the early and late relapse groups, respectively). Compared with patients who experienced late relapse, those with early relapse showed a higher prevalence of the following adverse prognostic factors: pT4, pN3, pStage IV, poor differentiation, depth of invasion ≥ 10 mm, and extra-nodal extension. Multivariable analysis revealed that early relapse was an independent adverse prognostic factor for both 5-year DSS and OS (average hazard ratios [AHRs]: 3.24 and 3.91, respectively). In the PS-matched cohort, patients who experienced early relapse showed less favorable 5-year DSS: 58% versus 30%, p < 0.0001 (AHR: 3.10 [2.69 − 3.57]) and OS: 49% versus 22%, p < 0.0001 (AHR: 3.32 [2.89 − 3.81]).ConclusionAfter adjustment for potential confounders and PS matching, early relapse was an adverse prognostic factor for survival outcomes in patients with OCSCC. Our findings may have significant implications for risk stratification.

The Prevalence of HPV in Oral Cavity Squamous Cell Carcinoma.

Human papillomavirus (HPV) is an important risk factor in a subset of head and neck squamous cell carcinomas (HNSCC), but the association with oral cavity squamous cell carcinomas (OCSCC) remains controversial. This study aimed to identify the prevalence of HPV infection in OCSCC. A systematic search on PubMed and EMBASE was performed, including articles assessing the prevalence of HPV-positive (HPV+) OCSCC published from January 2017 to December 2022. OCSCC was considered HPV+ by the detection of HPV DNA, HPV RNA, and/or p16 overexpression in the tumor mass. A meta-analysis was made determining the overall HPV+ OCSCC prevalence. We included 31 studies comprising 5007 patients from 24 countries. The study size ranged from 17 to 940 patients. The HPV+ OCSCC proportion variated widely and ranged from 0% to 37%. Tumors in the tongue were the predominant sublocation for HPV in the oral cavity. The meta-analysis revealed that the overall HPV+ OCSCC prevalence is 6% (95% CI; 3-10%), and only one study found HPV and OCSCC significantly associated. Thus, HPV may not be a necessary or a strong risk factor in OCSCC oncogenesis, and the possibility of a site misclassification of a mobile tongue with the root of the tongue cannot be excluded.