Post-operative intensity-modulated vs 3D conformal radiotherapy after conservative surgery for laryngeal tumours of the supraglottic region: a dosimetric analysis on 20 patients.

Objective: To perform a dosimetric comparison between intensity modulated radiotherapy (IMRT) and 3D conformal radiotherapy in patients with locally advanced (stage III and IV) tumours of the supraglottic region treated with conservative surgery and post-operative radiotherapy. Methods: An in-silico plan using a 3D conformal shrinking field technique was retrospectively produced for 20 patients and compared with actually delivered IMRT plans. Eighteen structures (arytenoids, constrictor muscles, base of tongue, floor of mouth, pharyngeal axis, oral cavity, submandibular glands and muscles of the swallowing functional units [SFU]) were considered. Results: IMRT allowed a reduction of maximum and mean doses to 9 and 14 structures, respectively (p < .05). Conclusions: IMRT achieved a reduction of unnecessary dose to the remnant larynx and the majority of surrounding SFUs. Further prospective analyses and correlations with functional clinical outcomes are required to confirm these dosimetric findings.

Oral Surgery and Osteoradionecrosis in Patients Undergoing Head and Neck Radiation Therapy: An Update of the Current Literature.

Osteoradionecrosis (ORN) is a serious long-term complication of head and neck radiotherapy (RT), which is often triggered by dental extractions. It results from avascular aseptic necrosis due to irradiated bone damage. ORN is challenging to treat and can lead to severe complications. Furthermore, ORN causes pain and distress, significantly reducing the patient's quality of life. There is currently no established preventive strategy. This narrative review aims to provide an update for the clinicians on the risk of ORN associated with oral surgery in head and neck RT patients, with a focus on the timing suitable for the oral surgery and possible ORN preventive treatments. An electronic search of articles was performed by consulting the PubMed database. Intervention and observational studies were included. A multidisciplinary approach to the patient is highly recommended to mitigate the risk of RT complications. A dental visit before commencing RT is highly advised to minimize the need for future dental extractions after irradiation, and thus the risk of ORN. Post-RT preventive strategies, in case of dento-alveolar surgery, have been proposed and include antibiotics, hyperbaric oxygen (HBO), and the combined use of pentoxifylline and tocopherol ("PENTO protocol"), but currently there is a lack of established standards of care. Some limitations in the use of HBO involve the low availability of HBO facilities, its high costs, and specific clinical contraindications; the PENTO protocol, on the other hand, although promising, lacks clinical trials to support its efficacy. Due to the enduring risk of ORN, removable prostheses are preferable to dental implants in these patients, as there is no consensus on the appropriate timing for their safe placement. Overall, established standards of care and high-quality evidence are lacking concerning both preventive strategies for ORN as well as the timing of the dental surgery. There is an urgent need to improve research for more efficacious clinical decision making.

Galectin-9 expression on tumour-associated immune cells is associated with favourable clinicopathological features and better outcomes in oral squamous cell carcinoma.

Introduction: Galectin-9, a ß-galactoside-binding protein, might be a potential target in cancer personalized therapy, but contradicting data exist regarding its prognostic significance in malignancy. Previous studies showed low or absent expression of galectin-9 on tumour cells of oral squamous cell carcinoma (OSCC); thus, we aimed to assess the prognostic impact of its expression on tumour-associated immune cells (TAICs). Material and methods: A retrospective analysis was conducted on 62 patients with OSCC. Tissue microarrays were constructed with chemo- and radiotherapy-naïve tissue samples and stained with anti-galectin-9 antibody. Cytoplasmic reactions in TAICs were counted as positive, and the percentage of galectin-9-positive cells was calculated. Results: The expression of galectin-9 was not associated with any demographic factors, other than diabetes mellitus type 2, for which there were lower levels of expression (p = 0.029). Higher levels of galectin-9 were associated with less locally advanced tumours (p = 0.023) and lack of nodal metastases (p = 0.014). Galectin-9 expression positively correlated with PD-L1 expression on TAICs (p = 0.009). Patients with > 50% galectin-9-positive cells were determined to have a superior 5-year overall survival (p = 0.029). Conclusions: Future studies are necessary to investigate the effects of galectin-9 on the tumour micro-environment, and galectin-9-targeted treatment may be considered, especially with its correlation to PD-L1 in OSCC.

Prospects of POLD1 in Human Cancers: A Review.

Cancer is the second leading cause of death globally, exceeded only by cardiovascular disease. Despite the introduction of several survival-prolonging treatment modalities, including targeted therapy and immunotherapy, the overall prognosis for the metastatic disease remains challenging. Therefore, the identification of new molecular biomarkers and therapeutic targets related to cancer diagnosis and prognosis is of paramount importance. DNA polymerase delta 1 (POLD1), a catalytic and proofreading subunit of the DNA polymerase δ complex, performs a crucial role in DNA replication and repair processes. Recently, germline and somatic mutations of the POLD1 gene have been acknowledged in several malignancies. Moreover, diversified POLD1 expression profiles have been reported in association with clinicopathological features in a variety of tumor types. With this review, we aim to summarize the current knowledge on the role of POLD1 in cancers. In addition, we discuss the future prospects and clinical applications of the assessment of POLD1 mutation and expression patterns in tumors.

Treatment of Reticular Oral Lichen Planus with Photodynamic Therapy: A Case Series.

OBJECTIVES: The aim of the study was to clinically evaluate the efficacy of photodynamic therapy in treatment of the reticular form of oral lichen planus (OLP). MATERIALS AND METHODS: Twenty patients aged 40-76, with 40 confirmed OLP lesions in total, underwent photodynamic therapy (PDT) following the authors' own protocol, which used 5% 5-aminolevulinic acid as a photosensitizer applied two hours prior to illumination with a diode lamp emitting light at 630 nm and 300 mW. The therapy comprised of 10 weekly illumination sessions and was clinically evaluated between its completion and the end of a 12-month follow-up. RESULTS: While the baseline mean size of all 40 lesions was 2.74 ± 3.03 cm2, it was 2.97 ± 3.4 cm2 for the 30 lesions on the buccal mucosa and 2.02 ± 1.32 cm2 for the remaining 10 on the gingiva and tongue. On completion of the therapy, 37 sites improved, including 14 showing complete remission. From that point, the mean size reduction of 56.2% (1.2 ± 1.4 cm2) rose to 67.88% (0.88 ± 1.3 cm2) 12 months later. CONCLUSIONS: The results suggest that ALA-mediated photodynamic therapy was effective for the reticular form of OLP and may become an optional or complementary treatment.

Prognostic Impact of Sarcopenia's Occurrence during Radiotherapy in Oropharyngeal Cancer Patients.

The current study aims to profile sarcopenic condition (both at baseline and developed during treatment) in oropharyngeal carcinoma (OPC) patients treated with curative radiotherapy (RT) +/- chemotherapy and to evaluate its impact on oncological outcomes and toxicity. A total of 116 patients were included in this retrospective single-center study. Sarcopenia assessment at baseline and at 50 Gy re-evaluation CT was obtained from two different methodologies: (i) the L3-skeletal muscle index (SMI) derived from the contouring of the cross-sectional area (CSA) of the masticatory muscles (CSA-MM); and (ii) the paravertebral and sternocleidomastoid muscles at the level of the third cervical vertebra (CSA-C3). Based on L3-SMI from CSA-MM, developing sarcopenic condition during RT (on-RT sarcopenia) was associated with worse progression-free survival (PFS) (p = 0.03) on multivariable analysis and a trend of correlation with overall survival (OS) was also evident (p = 0.05). According to L3-SMI derived from CSA-C3, on-RT sarcopenia was associated with worse PFS (p = 0.0096) and OS (p = 0.013) on univariate analysis; these associations were not confirmed on multivariable analysis. A significant association was reported between becoming on-RT sarcopenia and low baseline haemoglobin (p = 0.03) and the activation of nutritional counselling (p = 0.02). No significant associations were found between sarcopenia and worse RT toxicity. Our data suggest that the implementation of prompt nutritional support to prevent the onset of sarcopenia during RT could improve oncological outcomes in OPC setting.

VISTA H-Score Is Significantly Associated with a 5-Year DFS Rate in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer in the world. Despite its prevalence, it is often recognized in advanced stages (III or IV) when it has already spread to local lymph nodes. In this study, we investigate the V-domain Ig suppressor of T cell activation (VISTA) as a potential prognostic factor in OSCC. Tissue samples were collected from 71 oral squamous cell carcinoma patients to determine protein expression levels (using immunochemistry and the semi-quantitative H-score method). Moreover, RT-qPCR was additionally performed in 35 patients. Clinical factors in our cohort study had no impact on VISTA expression. However, VISTA expression is largely correlated with Il-33 levels in tumor cells and lymphocytes and with PD-L1 in tumor cells. The impact of VISTA expression on overall survival (OS) is rather limited, but in the case of a 5-year survival rate, a significant association has been proven. VISTA seems to be a rather weak clinicopathological marker but needs further evaluation in the context of survival. In addition, the potential of VISTA combination with Il-33 or PD-L1 should be further investigated in OSCC.

Neural Component of the Tumor Microenvironment in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive primary malignancy of the pancreas, with a dismal prognosis and limited treatment options. It possesses a unique tumor microenvironment (TME), generating dense stroma with complex elements cross-talking with each other to promote tumor growth and progression. Diversified neural components makes for not having a full understanding of their influence on its aggressive behavior. The aim of the study was to summarize and integrate the role of nerves in the pancreatic tumor microenvironment. The role of autonomic nerve fibers on PDAC development has been recently studied, which resulted in considering the targeting of sympathetic and parasympathetic pathways as a novel treatment opportunity. Perineural invasion (PNI) is commonly found in PDAC. As the severity of the PNI correlates with a poorer prognosis, new quantification of this phenomenon, distinguishing between perineural and endoneural invasion, could feature in routine pathological examination. The concepts of cancer-related neurogenesis and axonogenesis in PDAC are understudied; so, further research in this field may be warranted. A better understanding of the interdependence between the neural component and cancer cells in the PDAC microenvironment could bring new nerve-oriented treatment options into clinical practice and improve outcomes in patients with pancreatic cancer. In this review, we aim to summarize and integrate the current state of knowledge and future challenges concerning nerve-cancer interactions in PDAC.

Milk Formula Enriched with Sodium Butyrate Influences Small Intestine Contractility in Neonatal Pigs.

Butyrate, a by-product of gut bacteria fermentation as well as the digestion of fat in mother's milk, exerts a wide spectrum of beneficial effects in the gastrointestinal tissues. The present study aimed to determine the effects of sodium butyrate on small intestine contractility in neonatal piglets. Piglets were fed milk formula alone (group C) or milk formula supplemented with sodium butyrate (group B). After a 7-day treatment period, isometric recordings of whole-thickness segments of the duodenum and middle jejunum were obtained by electric field stimulation under the influence of increasing doses of Ach (acetylocholine) in the presence of TTX (tetrodotoxin) and atropine. Moreover, structural properties of the intestinal wall were assessed, together with the expression of cholinergic and muscarinic receptors (M1 and M2). In both intestinal segments (duodenum and middle jejunum), EFS (electric field stimulation) impulses resulted in increased contractility and amplitude of contractions in group B compared to group C. Additionally, exposure to dietary butyrate led to a significant increase in tunica muscularis thickness in the duodenum, while mitotic and apoptotic indices were increased in the middle jejunum. The expression of M1 and M2 receptors in the middle jejunum was significantly higher after butyrate treatment. The results indicate increased cholinergic signaling and small intestinal growth and renewal in response to feeding with milk formula enriched with sodium butyrate in neonatal piglets.

Alterations in key signaling pathways in sinonasal tract melanoma. A molecular genetics and immunohistochemical study of 90 cases and comprehensive review of the literature.

Sinonasal mucosal melanoma is a rare tumor arising within the nasal cavity, paranasal sinuses, or nasopharynx (sinonasal tract). This study evaluated 90 cases diagnosed in 29 males and 61 females with median age 68 years. Most tumors involved the nasal cavity and had an epithelioid morphology. Spectrum of research techniques used in this analysis includes targeted-DNA and -RNA next-generation sequencing, Sanger sequencing, fluorescence in situ hybridization and immunohistochemistry. Sinonasal melanomas were commonly driven by RAS (38/90, 42%), especially NRAS (n = 36) mutations and rarely (4/90, 4%) displayed BRAF pathogenic variants. BRAF/RAS mutants were more frequent among paranasal sinuses (10/14, 71%) than nasal (26/64, 41%) tumors. BRAF/RAS-wild type tumors occasionally harbored alterations of the key components and regulators of Ras-MAPK signaling pathway: NF1 mutations (1/17, 6%) or NF1 locus deletions (1/25, 4%), SPRED1 (3/25, 12%), PIK3CA (3/50, 6%), PTEN (4/50, 8%) and mTOR (1/50, 2%) mutations. These mutations often occurred in a mutually exclusive manner. In several tumors some of which were NRAS mutants, TP53 was deleted (6/48, 13%) and/or mutated (5/90, 6%). Variable nuclear accumulation of TP53, mirrored by elevated nuclear MDM2 expression was seen in >50% of cases. Furthermore, sinonasal melanomas (n = 7) including RAS/BRAF-wild type tumors (n = 5) harbored alterations of the key components and regulators of canonical WNT-pathway: APC (4/90, 4%), CTNNB1 (3/90, 3%) and AMER1 (1/90, 1%). Both, TERT promoter mutations (5/53, 9%) and fusions (2/40, 5%) were identified. The latter occurred in BRAF/RAS-wild type tumors. No oncogenic fusion gene transcripts previously reported in cutaneous melanomas were detected. Eight tumors including 7 BRAF/RAS-wild type cases expressed ADCK4::NUMBL cis-fusion transcripts. In summary, this study documented mutational activation of NRAS and other key components and regulators of Ras-MAPK signaling pathway such as SPRED1 in a majority of sinonasal melanomas.

The B7 family molecules in oral squamous cell carcinoma: a systematic review. Part I: B7-H1 (PD-L1) and B7-DC (PD-L2).

Introduction: Oral squamous cell carcinoma (OSCC) is the most common cancerous lesion in the oral cavity. During recent years, no significant reduction in the survival rate has been observed. Aim: To systematically review the literature and to summarise correlations between B7 family proteins and prognosis in OSCC. Material and methods: A systematic review of the literature about B7-H1 (PD-L1) and B7-DC (PD-L2) was carried out, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Thirty-six articles published before 22 May 2020 were included in the systematic review. Results: The biggest study group consisted of 305 patients and the smallest - 10 patients. PD-L1 proved to be a prognostic factor in patients with OSCC. Immunohistochemistry was the most commonly used diagnostic method. Conclusions: Any mutations in the gene encoding PD-L1 and quantitative or functional changes in the status of PD-L1 may be important in the prognosis of OSCC.

Intensity-Modulated Radiotherapy (IMRT) following Conservative Surgery of the Supraglottic Region: Impact on Functional Outcomes.

The aim of the present study was to investigate the role of intensity-modulated radiotherapy (IMRT) on the toxicity profile of patients treated with conservative surgery (CS) of the supraglottic (SG) region. Data on patients treated with CS and postoperative radiotherapy (PORT)-IMRT were prospectively collected. Results. In total, 20 patients were analyzed. Of these, six patients (35%) required the positioning of a temporary tracheostomy. The functional larynx preservation rate was 95%. Females had a higher risk of both endoscopic intervention and chondronecrosis, while the median age was significantly higher in patients requiring enteral nutrition. The incidence of long-term severe toxicities was lower in patients treated with IMRT than in the historical 3D-CRT cohort. Patients who had received PORT-IMRT achieved a lower rate of permanent laryngeal and swallowing dysfunctions. Overall, results from the comparison with the historical 3D-CRT cohort favor the IMRTs.

Association between Maternal Periodontitis and Development of Systematic Diseases in Offspring.

Periodontal disease (PD) is one of the most common oral conditions affecting both youths and adults. There are some research works suggesting a high incidence of PD in pregnant women. As an inflammatory disease of bacterial origin, PD may result in the activation of the pathways affecting the course and the pregnancy outcome. The authors, based on the literature review, try to answer the PICO question: Does maternal periodontitis (exposure) influence the incidence of complications rates in pregnancy and the development of systemic diseases in childhood and adult offspring (outcome) in the humans of any race (population) compared to the offspring of mothers with healthy periodontium (comparison)? The authors try to describe the molecular pathways and mechanisms of these interdependencies. There is some evidence that maternal periodontitis may affect the pregnancy course and outcome, resulting in preeclampsia, preterm delivery, vulvovaginitis and low birth weight. It can be suggested that maternal periodontitis may affect offspring epigenome and result in some health consequences in their adult life.

Current Challenges in Head and Neck Cancer Management.

More than 500,000 new cases of head and neck cancer (HNC) occur each year worldwide [...].

Indication to post-operative radiotherapy for oral cavity squamous cell carcinoma: what's new in the depth of infiltration (DOI) era?

OBJECTIVE: The last edition of the American Joint Committee on Cancer (AJCC eighth) has introduced the depth of infiltration (DOI) as a new prognostic parameter in oral cavity squamous cell carcinomas (OCSCCs). The aim of this study is to analyze the impact of stage migration on the indication to post-operative radiotherapy (PORT). METHODS: OCSCCs treated at two institutions between 2014 and 2019 were retrieved. As per the AJCC eighth, only pT3 primarily OCSCCs were considered; availability of the pathologic specimen was a further inclusion criterion. Risk factors considered for PORT were: pT3-pT4, nodal involvement, positive/close surgical margins, perineural and lymph vascular invasion. RESULTS: 149 patients staged as pT3 AJCC eighth were included. A four-fold increase in the number of patients staged as pT3 from the seventh to the eighth AJCC was found. Stage migration to pT3 was equally due to the downstaging from former pT4 (38%) and upstaging of former pT1-pT2 (35%). Considering the former pT1-pT2 53 patients, 13 (25%) had no risk factors for PORT other than DOI. Among 25 cases with former pT1-pT2 and negative lymph nodes, no additional risk factors were found in 11 (44%). CONCLUSION: 90% of patients had at least one risk factor besides DOI and would have received PORT also according to the AJCC seventh; notably, of former pT1-pT2N0, half of them have been upstaged to pT3 in the current TNM classification. The role of PORT in this cohort of patients has not been clarified yet. ADVANCES IN KNOWLEDGE: Other-than-DOI risk factors leading to PORT indication are highly prevalent in OCSSC patients classified as pT3 per the latest AJCC TNM staging system and should therefore be considered for a comprehensive oncological assessment.

Machine Learning for Head and Neck Cancer: A Safe Bet?-A Clinically Oriented Systematic Review for the Radiation Oncologist.

BACKGROUND AND PURPOSE: Machine learning (ML) is emerging as a feasible approach to optimize patients' care path in Radiation Oncology. Applications include autosegmentation, treatment planning optimization, and prediction of oncological and toxicity outcomes. The purpose of this clinically oriented systematic review is to illustrate the potential and limitations of the most commonly used ML models in solving everyday clinical issues in head and neck cancer (HNC) radiotherapy (RT). MATERIALS AND METHODS: Electronic databases were screened up to May 2021. Studies dealing with ML and radiomics were considered eligible. The quality of the included studies was rated by an adapted version of the qualitative checklist originally developed by Luo et al. All statistical analyses were performed using R version 3.6.1. RESULTS: Forty-eight studies (21 on autosegmentation, four on treatment planning, 12 on oncological outcome prediction, 10 on toxicity prediction, and one on determinants of postoperative RT) were included in the analysis. The most common imaging modality was computed tomography (CT) (40%) followed by magnetic resonance (MR) (10%). Quantitative image features were considered in nine studies (19%). No significant differences were identified in global and methodological scores when works were stratified per their task (i.e., autosegmentation). DISCUSSION AND CONCLUSION: The range of possible applications of ML in the field of HN Radiation Oncology is wide, albeit this area of research is relatively young. Overall, if not safe yet, ML is most probably a bet worth making.

The Growth Factors in Advanced Platelet-Rich Fibrin (A-PRF) Reduce Postoperative Complications after Mandibular Third Molar Odontectomy.

Surgical removal of impacted mandibular third molars constitutes one of the most frequently performed procedures within oral surgery. This surgery procedure is associated with many post-operative complications. Advanced platelet-rich fibrin (A-PRF) belongs to the second generation of platelet concentrates and is rich in numerous growth factors. The aim of this study was to assess the influence of A-PRF on selected clinical features following the surgical removal of impacted mandibular third molars. The research was conducted on 100 generally healthy patients, who underwent a lower third molar odontectomy in Department of Oral Surgery, Medical University of Gdansk, Poland, between 2018 and 2019. The research group consisted of 50 patients (immediate A-PRF socket filling) and control group (50 patients without A-PRF socket filling). During the study, the following clinical features were assessed: pain (visual analog scale), analgesics intake, the presence of trismus, edema, hematomas within the surrounding tissues (e.g., cheek), prevalence of pyrexia, dry socket, secondary bleeding, presence of hematomas, skin warmth in the post-operative area, and bleeding time observed by the patient were analyzed on the 3rd, 7th, and 14th day after the procedure. There was a significant association between A-PRF socket filling and pain intensity, the analgesics intake, trismus, and edema on the 3rd and the 7th day (p < 0.05). The presence of hematomas and skin warmth on the 3rd day after the surgery (p < 0.05) were also statistically associated with A-PRF use. The study showed that in reducing the incidence of postoperative complications, A-PRF was more important than the position of the tooth or the duration of the procedure. The growth factors in A-PRF reduce postoperative complications, such as pain, trismus, edema, analgesics intake, presence of hematomas, and skin warmth, after mandibular wisdom teeth odontectomy.

Local/Topical Antibiotics for Peri-Implantitis Treatment: A Systematic Review.

Most studies indicate that the mechanical removal of the bacterial biofilm from the implant surface is the central goal of peri-implantitis therapy. However, controversial results in the treatment of peri-implantitis have led to the consideration of additional strategies that include surgical approaches and chemical adjuvants. Local/topical antibiotics, such as minocycline, azithromycin, tetracycline, amoxicillin, doxycycline, and metronidazole, may improve the efficacy of the definitive treatment of the disease, but the lack of conclusive findings prevents their use in clinical practice. This systematic review aimed to evaluate the effect of local/topical antibiotics for peri-implantitis treatment. Randomised controlled studies (RCT) on patients with peri-implantitis and comparing the efficacy of local/topical antibiotics vs. placebo or mechanical debridement were included. A systematic search strategy was carried out using three registered databases (PubMed, Web of Science, and Scopus). RoB2 was used to assess risk of bias. Five RCTs were identified (n = 250 patients and 333 implants). Contrast results emerged among the included studies, and a high heterogeneity level was observed. Risk of bias revealed some concerns for three studies out of five, while one study was judged at high risk. Only one study analysed the limitations of its findings. Overall, local antibiotic use can be considered a valid approach in the treatment of peri-implantitis. Therefore, future long-term clinical trials with standardised protocols and antibiotics with similar biological activity profiles should be tested to achieve a valid and definitive conclusion.

The Impact of Post-Operative Radiotherapy in Early Stage (pT1-pT2N0M0) Oral Tongue Squamous Cell Carcinoma in Era of DOI.

Background: This study investigated the role of depth of infiltration (DOI) as an independent prognosticator in early stage (T1-T2N0M0) oral cavity tumors and to evaluate the need of postoperative radiotherapy in the case of patients upstaged to pT3 for DOI > 10 mm in the absence of other risk factors. Methods: We performed a retrospective analysis on patients treated with surgery and re-staged according to the 8th edition of malignant tumors classification (TNM). The role of DOI as well as other clinical/pathological features was investigated at both univariable and multivariable analyses on overall survival (OS), disease free survival (DFS), relapse free survival (RFS), and local RFS. Results: Among the 94 included patients, 23 would have been upstaged to pT3 based on DOI. Multivariable analysis showed that DOI was not an independent prognostic factor for any of the considered outcomes. The presence of perineural invasion was associated with a significant worse RFS (p = 0.02) and LRFS (p = 0.04). PORT was found to be significantly associated with DFS (p = 0.04) and RFS (p = 0.06). Conclusions: The increasing DOI alone was not sufficient to impact the prognosis, and therefore, should not be sufficient to dictate PORT indications in early-stage patients upstaged on the sole basis of DOI.

High PD-L1 Expression on Tumor Cells Indicates Worse Overall Survival in Advanced Oral Squamous Cell Carcinomas of the Tongue and the Floor of the Mouth but Not in Other Oral Compartments.

The markers of the tumor microenvironment (TME) are promising prognostic and predictive factors in oral squamous cell carcinoma (OSCC). The current study aims to analyze the immunohistochemical expression of programmed cell death-ligand 1 (PD-L1) and interleukin-33 (IL-33) in a cohort of 95 chemonaïve OSCCs. PD-L1 and IL-33 were assessed separately in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs). High PD-L1 expression in TILs was associated with better overall survival (OS) in univariate analysis. Tumors localized in the floor of the oral cavity and tongue tended to have a lower percentage of PD-L1-positive TCs when compared to other locations. PD-L1 expression on TCs had no prognostic significance when the whole cohort was analyzed. However, along with the T descriptor (TNM 8th), it was included in the multivariable model predicting death in carcinomas of the floor of the oral cavity and tongue (HR = 2.51, 95% CI = 1.97-5.28). In other locations, only nodal status was identified as an independent prognostic factor in multivariate analysis (HR = 0.24, 95% CI = 0.08-0.70). Expression of IL-33 had no impact on survival, but it was differently expressed in various locations. In conclusion, the prognostic significance of PD-L1 in oral cancer depends on the tumor site and type of cell expressing immune checkpoint receptor (TCs vs. TILs).