OBJECTIVE: The pathogenesis of oral cavity cancers is complex. We tested the hypothesis that oral microbiota dysbiosis is associated with oral cavity cancer.
METHODS: Patients with primary oral cavity cancer who met the inclusion and exclusion criteria were included in the study. Matching healthy individuals were recruited as controls. Data on socio-demographic and behavioral factors, self-reported periodontal measures and habits, and current dental status were collected using a structured questionnaire and periodontal chartings. In addition to self-reported oral health measures, each participant received a standard and detailed clinical examination. DNA was extracted from saliva samples from patients and healthy controls. Next-generation sequencing was performed by targeting V3-V4 gene regions of the 16 S rRNA with subsequent bioinformatic analyses.
RESULTS: Patients with oral cavity cancers had a lower quality of oral health than healthy controls. Proteobacteria, Aggregatibacter, Haemophilus, and Neisseria decreased, while Firmicutes, Bacteroidetes, Actinobacteria, Lactobacillus, Gemella, and Fusobacteria increased in oral cancer patients. At the species level, C. durum, L. umeaens, N. subflava, A. massiliensis, and V. dispar were significantly lower, while G. haemolysans was significantly increased (p < 0.05). Major periodontopathogens associated with periodontal disease (P. gingivalis and F.nucleatum) increased 6.5- and 2.8-fold, respectively.
CONCLUSIONS: These data suggested that patients with oral cancer had worse oral health conditions and a distinct oral microbiome composition that is affected by personal daily habits and may be associated with the pathogenicity of the disease and interspecies interactions.
CONCLUSIONS: This paper demonstrates the link between oral bacteria and oral cancers, identifying mechanistic interactions between species of oral microbiome.

Introduction: Pectoralis major myo-cutaneous (PMMC) flap continues to be a widely used tool to reconstruct oral cavity defects. But an unreliable and unstable vascular supply can lead to complications like flap loss, Oro-cutaneous fistula and wound dehiscence. Preservation of the lateral thoracic artery (LTA) has been suggested to improve the vascularity of the skin paddle. The present study aspires to compare the complications and flap related outcomes after preserving or sacrificing the LTA while reconstructing oral cavity defects with bi-folded PMMC flap. Materials and Methods: Retrospective analysis of the data of 61 male patients who were reconstructed with bi-folded PMMC flaps between January 2022 and September 2022 was done. 36 patients were reconstructed using a PMMC flap where the LTA was sacrificed, whereas in 25 patients the LTA was preserved. Data was analyzed in terms of patient factors and flap related complications. Results: The overall complication rate including major/minor complications was 44.26% with flap detachment at 22.95% being the commonest complication observed. 13.11% patients developed an Oro-cutaneous fistula and partial and complete flap loss were seen in 9.83% and 4.91% respectively. LTA preservation was significantly associated with only decreased flap detachment rates (p value < 0.05). No significant association was noticed between other flap related complications and LTA preservation. Conclusion: Reconstructing larger defects with a PMMC flap where the LTA is preserved can help improve the vascularity of the flap and decrease various major/minor flap related complications.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s12070-023-04123-3.

We prospectively assessed acute and late toxicity in post-operative oral cavity squamous cell carcinoma (PO-OCSCC) treated with adjuvant dysphagia optimized intensity-modulated radiotherapy (Do-IMRT) versus standard IMRT (S-IMRT).
Fifty-six patients of PO-SCC without indications of concurrent chemotherapy were alternatively allocated to adjuvant Do-IMRT (n = 28) versus S-IMRT (n = 28) arms. High- and low-risk planning target volume received 60 and 54 Gy, respectively, in 30 fractions over 6 weeks. Dysphagia aspiration-related structures (DARS) were contoured in both arms. While dosimetric constraints were given in Do-IMRT arm, doses to DARS were only observed without dose constraints in S-IMRT arm. Acute and late toxicity were assessed by common terminology criteria for adverse events (CTCAE) v5.0 and RTOG criteria, respectively.
The primary site of disease was buccal mucosa (64% vs. 53%) and oral tongue (21% vs. 32%), in Do-IMRT and S-IMRT, respectively. The mean doses to DARS was significantly less with Do-IMRT (all p < 0.001) as compared to S-IMRT. Median follow-up was 24.2 months. Grade ≥2 oral pain was less in the Do-IMRT arm (50% vs. 78.6%, p = 0.05). Grade ≥2 late dysphagia at 2 years were significantly less in Do-IMRT arm (0% vs. 17.9%, p = 0.016). Two-year locoregional control was 89.2% in Do-IMRT and 78.5% in S-IMRT (p = 0.261).
DARS can be spared in PO-OCSCC patients treated with Do-IMRT without compromising coverage of the target volumes. Limiting doses to DARS leads to lesser acute and late toxicity without compromising locoregional control.

UNASSIGNED: The present study examines the role of demographic and pathological features of primary tumours in predicting neck metastasis in early oral cavity cancers, which has been a matter of debate.
UNASSIGNED: A single-centre, retrospective, institution review was conducted of all the patients presented to our centre from January 2014 to December 2021. Patient characteristics were compared between the two lymph node groups (lymph node positive and lymph node negative) and significant prognostic factors were determined.
UNASSIGNED: A total of 462 oral squamous cell carcinoma (OSCC) patients were included, 407 male and 55 female. Tobacco chewing (59.2%) was a major habit with buccal mucosa (49.5%) and tongue (44.8%) as primary sites. The majority of the patient\'s histology was of SCC (96.8%) with grade II (moderately differentiated, 74.5%). Univariate logistic regression analysis to predict lymph node metastasis showed pT size (< 0.001), LVI (< 0.001), and PNI (< 0.001) as significant tumor characteristics. On multivariate, pT size (OR-1.58, P - 0.0001) and LVI (OR-19.70, P - 0.0001) were reported to be statistically significant to predict lymph node metastasis.
UNASSIGNED: Reporting and studying the clinico-pathological features of primary tumors can give vital information in predicting the neck node metastasis in OSCC patients.

UNASSIGNED: Follow-up of patients treated for head and neck cancer is an important part of the overall treatment. Oral cancers are one of the leading causes of dysphagia. Swallowing dysfunction occurs owing to the disease itself, its predisposing factors, and the treatment. This study aims to evaluate swallowing dysfunction in patients with oral cavity cancers.
UNASSIGNED: This prospective study was carried out in a tertiary care hospital institution. Thirty patients with T3, T4 oral cancers were evaluated using institutional dysphagia score and fiber optic endoscopic evaluation of swallowing (FEES) (Penetration-Aspiration Scale, Yale Pharyngeal Residue Scale) before treatment, after surgery, and after adjuvant therapy.
UNASSIGNED: Advanced-stage tumor, larger resections, and adjuvant therapy are risk factors for dysphagia postoperatively. Although the dysphagia score is our institutional score, the results are promising, that is, 10 % of patients having symptoms at baseline evaluation, which increased to 60% and 70% after surgery and adjuvant radiotherapy respectively. Our study findings of the Penetration Aspiration Scale are 13% aspiration rate at the baseline evaluation, which increased to 57% and 73% after surgery and after adjuvant radiotherapy, respectively, and these results are consistent with those of other report studies. The Vallecular Residual Scale showed that there was a significant association between three different timelines and demonstrated dysphagia among study subjects.
UNASSIGNED: Subjective and objective assessment of swallowing dysfunction before and after the treatment of head and neck cancers is underreported and underrecognized. Most of the patients in our study had significant swallowing impairment after treatment. FEES is a very effective procedure to diagnose dysphagia and will help in incorporating better preventative and rehabilitative measures.

When presenting with major pathological risk factors, adjuvant radio-chemotherapy for oral cavity cancers (OCC) is recommended, but the addition of chemotherapy to radiotherapy (POCRT) when only minor pathological risk factors are present is controversial. A systematic review following the PICO-PRISMA methodology (PROSPERO registration ID: CRD42021267498) was conducted using the PubMed, Embase, and Cochrane libraries. Studies assessing outcomes of POCRT in patients with solely minor risk factors (perineural invasion or lymph vascular invasion; pN1 single; DOI ≥ 5 mm; close margin < 2−5 mm; node-positive level IV or V; pT3 or pT4; multiple lymph nodes without ENE) were evaluated. A meta-analysis technique with a single-arm study was performed. Radiotherapy was combined with chemotherapy in all studies. One study only included patients treated with POCRT. In the other 12 studies, patients were treated with only PORT (12,883 patients) and with POCRT (10,663 patients). Among the patients treated with POCRT, the pooled 3 year OS rate was 72.9% (95%CI: 65.5−79.2%); the pooled 3 year DFS was 70.9% (95%CI: 48.8−86.2%); and the pooled LRFS was 69.8% (95%CI: 46.1−86.1%). Results are in favor of POCRT in terms of OS but not significant for DFS and LRFS, probably due to the heterogeneity of the included studies and a combination of different prognostic factors.

BACKGROUND: Persistent human papillomavirus (HPV) infection is an important risk factor for a subset of head and neck cancers (HNCs). However, estimates of the HPV-attributable fraction of oropharyngeal cancers vary greatly, and the proportion is increasing. Growing evidence indicates smaller proportions of oral cavity and laryngeal cancers are also HPV-attributable, but this requires further investigation. The primary objective of the BROADEN study is to estimate the fraction of HNCs attributable to HPV in selected European and Asian countries by anatomic site. Secondary objectives are to determine HPV genotypes involved and to describe primary tumor and patient characteristics by HPV status.
METHODS: BROADEN is a non-interventional, cross-sectional study of patients with HNC in China, France, Germany, Italy, Japan, Portugal, and Spain. The HPV-attributable HNC fraction will be determined within pre-defined time-periods (2008-2009, 2013-2014 [China only], 2018-2019). Approximately 9000 patients from an estimated 90 hospitals with reference HNC diagnostic units and local reference pathology laboratories will participate. Sample size estimates were generated by grouped anatomic site (oropharynx, oral cavity, nasopharynx, hypopharynx, and larynx) and country. HPV testing (HPV-DNA and p16 immunohistochemistry [IHC]) will be performed at a central laboratory on formalin-fixed paraffin-embedded tissue samples. All HPV-DNA-positive samples and HPV-DNA-negative/p16 IHC-positive samples, plus 10% of remaining HPV DNA-negative (control) samples will be tested for HPV mRNA.
CONCLUSIONS: BROADEN is a large global epidemiologic study to estimate current and recent past HPV burden in oropharyngeal and non-oropharyngeal HNCs. BROADEN is expected to provide robust estimates of HPV attributability by anatomic site in participating countries.

OBJECTIVE: The space comprised between tumor and neck lymph nodes (T-N tract) is one of the main routes of tumor spread in oral cavity tumors. Aim of the study was to investigate the impact of T-N tract involvement on the postoperative radiotherapy (PORT) outcomes.
METHODS: Patients (pts) treated between 2000 and 2016 with indication to PORT were retrospectively retrieved. Inclusion criteria were: (a) locally advanced tumors of the oral cavity, (b) who received with indication to PORT (c) with a minimum follow-up of six months.
RESULTS: One hundred and fifty-seven pts met the inclusion criteria (136 pts treated with PORT and 21 pts not treated with PORT). In the PORT cohort, the T-N tract involvement had no impact on both OS (p = .09) and LRFS (p = .2). Among the non-PORT cohort, both OS (p = .007) and LRFS (p = .017) were worse for pts with positive T-N tract compared to those with negative T-N tract. PORT improved both OS (p = .008) and LRFS (p = .003) in pts with positive T-N tract but not in those with negative T-N tract (p = .36 and p = .37, respectively).
CONCLUSIONS: Our results suggest that involvement of T-N tract should be considered as prognostic factors informing the indication to PORT.

To determine effects of reconstruction in advanced oral cavity cancers in achieving a quality of life (QOL), which can help patients to cope with their routine day to day activity. A Cross sectional analysis involving 32 patients of stage III and IV oral cavity cancers already operated in the department of otolaryngology and head and neck surgery was carried out. All these patients had resection of their tumors along with reconstruction. Patients who consented for QOL assessment and follow up through personal visit and telephonic interviews were included in the study. Voice related quality of life; Swallowing related QOL; overall Quality of life (WHO QOL BREF II) and disability assessment scale (WHO DAS II) were used for assessing the various QOL parameters during post-operative period. Patients with stage T3 tumors had better QOL compared to patients with T4 stage tumors. Patients who had reconstruction with free flaps had better QOL compared to those with Pectoralis Major myocutaneous (PMMC) flaps or those reconstructed with combinations of flaps involving delto-pectoral flaps or local flaps along with a free flap or PMMC. Patients with lower stage tumors have better QOL even after reconstruction. If available, free flaps should be preferred over local flaps. Delto-pectoral flaps should be a less preferred option in terms of QOL. Every patient should be counseled accordingly while any reconstruction plan is included in the management of cancers of oral cavity.

The aim of our study was to evaluate the predictive ability of the American Joint Committee Cancer (AJCC) eighth edition (AJCC8) staging system for oral cavity cancers and validate these changes rendering the hypothesis of improving prognostication. We conducted a retrospective study including all oral cavity squamous cell carcinoma patients visiting our tertiary center from 2012 to 2015, staged as per the AJCC seventh edition (AJCC7) and AJCC8 systems. Stage-specific disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Concordance index (CI) and Akaike information criterion (AIC) were used to calculate the predictive accuracy of the both systems. The study sample consisted of 863 subjects followed up for a median of 24 months. Buccal mucosa complex (BMC) was the most common site (n = 496). We observed a 25.8% (n = 222) overall upstaging in the eighth edition, significantly seen in early tongue cancers (TCs) (Stage I) and advanced BMC cancers (Stage III). An increase in CI and reduction in AIC scores were indicative of a superior predictive accuracy for the eighth edition in assessing DFS (confidence interval [CI*] = 0.650-0.654; AIC = 3,022-3,014) and OS (CI* = 0.643-0.648; AIC = 2089-2086) across all stages. The accuracy was higher for TCs as compared to BMC. Although not statistically significant, we observed an increase in soft risk factors at higher stages in the eighth edition as compared to its predecessor. We concluded that the AJCC8 has a higher predictive accuracy than the AJCC7 edition, making it a reliable prognosticative tool.