Prognostic outcomes of oral squamous cell carcinoma derived from proliferative verrucous leukoplakia: A systematic review.

OBJECTIVE: This study aimed to evaluate prognostic outcomes of PVL-derived oral squamous cell carcinomas (P-OSCC) based on recurrence, new primary tumour, metastasis and survival information. STUDY DESIGN: Five databases and grey literature were searched electronically with the following main keywords (proliferative verrucous leukoplakia, squamous cell carcinoma and malignant transformation) to answer the following review question: 'Are survival outcomes for P-OSCC worse?' based on the PECOS principle. The Joanna Briggs Institute Critical Appraisal tool was used to identify possible biases and assess the quality of each of the primary studies. RESULTS: A total of 21 articles met the inclusion criteria, and the results of this systematic review suggest that P-OSCC can recur and generate new primary tumours; however, metastases are rare. Thus, most patients remain alive for an average period of 5 years. CONCLUSION: Apparently, P-OSCC has better clinical prognostic characteristics than conventional OSCC. There is a lack of information on the main prognostic outcomes of P-OSCC; therefore, specific studies must be performed to achieve a better comparison between P-OSCC and conventional OSCC progression.

Low-grade fibromyxoid sarcoma in labial mucosa: Report of a rare case in a pediatric patient.

Low-grade fibromyxoid sarcoma (LGFMS) is a malignant neoplasm of soft tissue, which occurs mainly in extremities. In this study, we described a rare case of LGFMS arising in the labial mucosa, in a 7-year-old male patient, who presented a painless multilobulated growth with an evolution time of 12 months. An incisional biopsy was performed and microscopic examination revealed a proliferation of bland regular spindle cells in an alternating myxoid and hyalinized stroma. The tumor cells showed a strong cytoplasmic immunoreactivity for MUC4 and low cell proliferation index measured by Ki-67 antibody. The diagnosis of LGFMS was established and the patient was referred for surgical treatment at a pediatric oncology hospital.

A rare case of squamous cell carcinoma of the gingiva: A diagnostic challenge.

BACKGROUND: Oral squamous cell carcinoma (OSCC) of the gingiva represents less than 6% of intraoral carcinomas. CASE REPORT: A 51-year-old male patient presented with a history of a symptomatic red spot with periods of remission and recurrence in the mandibular gingiva. On clinical examination red and white areas were observed in the gingiva, particularly around the left lower molars. Diagnosis of gingival lichen planus was suspected and topical corticosteroids was prescribed. A good clinical response was observed with reduction of symptom. The patient remained in regular follow-up and after 9 months, the lesion suddenly changed, became ulcerated and diagnosis of OSCC was established. CONCLUSION: The clinical manifestation of OSCC can eventually mimic other even more common lesions of the oral mucosa, highlighting the importance of considering OSCC as differential diagnosis of any unexplained and persistent lesion in the oral cavity.

Impact of head and neck radiotherapy on the longevity of dental adhesive restorations: A systematic review and meta-analysis.

STATEMENT OF PROBLEM: Established restorative protocols for patients after head and neck radiotherapy are lacking, increasing the failure rates of dental adhesive restorations. PURPOSE: The purpose of this systematic review and meta-analysis was to analyze the evidence regarding the impact of head and neck radiotherapy on the longevity of dental adhesive restorations. MATERIAL AND METHODS: A search was performed using PubMed, Scopus, and Embase in May 2018 (updated in November 2020). Data extraction was performed regarding the percentage of restoration failure among dental adhesive materials, including glass ionomer cements, resin-modified glass ionomer cements, and composite resins. Risk of bias was assessed by the meta-analysis of statistics assessment and review instrument (MAStARI). Confidence in cumulative evidence was evaluated by the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. RESULTS: Four studies met the inclusion criteria. All included studies were classified as having a moderate risk of bias and reported results regarding class V restorations. Overall, composite resins presented lower failure rates at 2 years (30%) when compared with resin-modified glass ionomer (41%) and glass ionomer cements (57%). Meta-analysis showed that the risk of failure with glass ionomer cements was greater than with resin-modified glass ionomer cements (RR: 1.71, P<.001). Composite resins presented lower risk of failure when compared with glass ionomer (RR: 2.29, P<.001) and resin-modified glass ionomer cements (RR: 1.30, P=.03). Three studies reported results regarding fluoride compliance, which had a negative effect on the survival rates of glass ionomer and resin-modified glass ionomer cements and a positive effect on composite resin restorations. CONCLUSIONS: The results suggest that composite resin restorations associated with fluoride gel compliance seems to be the best alternative for restoring class V lesions in patients after head and neck radiotherapy. However, the results showed moderate certainty of evidence, which justifies the need for more randomized clinical trials regarding this subject.

Extraoral photobiomodulation for prevention of oral and oropharyngeal mucositis in head and neck cancer patients: interim analysis of a randomized, double-blind, clinical trial.

PURPOSE: To assess the safety and efficacy of prophylactic extraoral photobiomodulation (PBM) for the prevention of oral and oropharyngeal mucositis (OM) on clinical outcomes and survival in patients with oral cavity and oropharyngeal squamous cell carcinoma (OOPSCC). METHODS: OOPSCC patients who received radiotherapy (RT) were prospectively randomized to two groups: prophylactic extraoral PBM and placebo. OM grade (NCI), pain (VAS), analgesia, and anti-inflammatory prescriptions were assessed weekly. Quality of life questionnaires (QoL) were performed at the first and last day of RT. Following RT, participants were evaluated quarterly for oncological outcomes follow-up. RESULTS: Fifty-five patients met the inclusion criteria. The first occurrence of OM was observed at week 1, for the placebo group (p = 0.014). Later, OM onset and severity was observed for the PBM group, with first occurrence at week 2 (p = 0.009). No difference in severe OM incidence was observed (p > 0.05). Lower mean pain score was noted at week 7 for the PBM group (2.1) compared to placebo group (4.5) (p = 0.009). Less analgesics (week 3; p = 0.009/week 7; p = 0.02) and anti-inflammatory prescription (week 5; p = 0.0346) were observed for the PBM group. Better QoL scores were observed for the PBM group at last day of RT (p = 0.0034). No difference in overall survival among groups was observed in 1 year of follow-up (p = 0.889). CONCLUSION: Prophylactic extraoral PBM can delay OM onset, reduce pain, and reduce analgesic and anti-inflammatory prescription requirements. Extraoral PBM was associated with better QoL. There was no evidence of PBM impact on oncological outcomes. TRIAL REGISTRATION: TRN:RBR-4w4swx (date of registration: 01/20/2020).

Patterns of oral mucositis in advanced oral squamous cell carcinoma patients managed with prophylactic photobiomodulation therapy-insights for future protocol development.

To characterize oral sites affected by radiation-induced oral mucositis (OM) and related clinical outcomes in oral cancer patients subjected to prophylactic photobiomodulation therapy (PBMT). This study included advanced oral squamous cell carcinoma (OSCC) patients treated with prophylactic PBMT for OM. The site distribution of OM, OM grading (CTCAE NCI, Version 4.0, 2010), OM-related pain (VAS), analgesic protocol (WHO Analgesic Ladder), and use of enteral nutrition were evaluated weekly during treatment. Data analysis was performed using descriptive statistics expressed as median values and percentages. A total of 145 OSCC patients were included. OM most frequently affected the lateral border of the tongue (44.1%), buccal mucosa (37.2%), and labial mucosa (33.8%). Keratinized oral mucosa sites, including the tongue dorsum (6.21%), retromolar trigone (8.3%), and hard palate (2.76%), were less frequently affected. Peak OM scores were observed at weeks 5, 6, and 7, with severe OM (NCI grades 3 and 4) rates of 11%, 20%, and 25%, respectively. The cumulative occurrence of severe OM was 23%, which developed as early as week 3 and as late as week 7. The highest mean value of OM-related pain (2.7) was observed at the sixth week, and 13.8% of the patients required feeding support. This study showed, compared with studies that did not provide PBMT, reduced severity of mucositis, reduced pain and analgesic use, and reduced tube feeding in patients treated with PBMT. OM involving keratinized and non-keratinized surfaces should be included in the prophylactic PBMT to reduce severe OM in future studies.

Laser excision of oral leukoplakia: Does it affect recurrence and malignant transformation? A systematic review and meta-analysis.

Oral leukoplakia (OL) is a white lesion with high potential of recurrence and malignant transformation. The variable clinical and histopathological features of OL may potentially impact both treatment and prognosis. Current literature shows that post treatment rates of recurrence and malignant transformation vary widely. The use of surgical lasers have been proposed with the objective of improving outcomes. We performed a systematic review and a comprehensive meta-analysis dedicated to pooling the rates of recurrence and malignant transformation of OL lesions treated using the main types of surgical lasers available. Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 36 articles met the inclusion criteria. Selected studies included OL lesions that were treated by evaporation or excision using Nd:YAG laser, Er:YAG laser, CO2 laser, KTP laser, or diode laser. The results of this systematic review and meta-analysis suggest that surgical laser excision of OL may decrease recurrence rates but have no effect on the malignant transformation of OL when compared with conventional treatments.

Global frequency and distribution of head and neck cancer in pediatrics, a systematic review.

BACKGROUND: Incidence and mortality rates of childhood cancer represent a global public health issue, however, the worldwide prevalence of head and neck cancer in pediatric patients (HNCPP) is still unknown. Therefore, this study aimed to describe the frequency and distribution of HNCPP worldwide. METHODS: A specific search strategy was performed using MEDLINE, Scopus, and EMBASE to include studies based on hospital records, national cancer registries, and pathology files. Studies quality was assessed using the risk of bias checklist of the Joanna Briggs Institute Critical Appraisal. RESULTS: Nineteen publications (15,970 cases) were included. Global frequency ranged from 0.25 % to 15 %. Male patients older than 10 years of age were most affected by lymphomas, followed by carcinomas and sarcomas. Non-Hodgkin lymphoma, Hodgkin lymphoma, rhabdomyosarcoma, thyroid carcinoma, and nasopharyngeal carcinoma were the main histopathological subtypes. Neck/lymph nodes were anatomical hotspots. CONCLUSIONS: This HNCPP global overview may guide secondary prevention strategies and future etiological studies.

The impact of radiation caries in the quality of life of head and neck cancer patients.

PURPOSE: The objective of this multicentre study was to verify the relationship between the scores of quality of life (QoL) and the decayed, missing and filled teeth (DMFT) and radiation caries (RC) in patients treated with radiation therapy (RT) for head and neck cancer, and through this to determine if RC is capable of causing a significant decrease in the QoL. METHODS: One hundred patients were divided into 2 groups: patients with at least 1 year of RT completion who developed RC (study group, n = 50); and patients with at least 1 year of RT completion who did not develop RC (control group, n = 50). All patients answered the Brazilian-Portuguese version of the University of Washington quality of life (UW-QoL) questionnaire, which was divided into physical and social-emotional functioning domains and evaluated the DMFT index score. RESULTS: The mean score of QoL was 927.2 in the control group and 878.1 in the study group (P = 0.24). The mean score of DMFT was 30.5 in the study group and 20.7 in the control group (P = 0.001). The items recreation and saliva, which belong to the physical function domain, showed a statistically significant difference between the study and control groups (P = 0.031 and P = 0.047, respectively). Saliva was the item with the higher number of patient complaints in both groups. CONCLUSION: RC had a negative impact on the QoL of HNC patients.

Is photobiomodulation therapy effective in reducing pain caused by toxicities related to head and neck cancer treatment? A systematic review.

Photobiomodulation therapy (PBMT) has been considered an effective method for preventing and managing certain cancer-related toxicities in head and neck cancer (HNC) patients treated with radiotherapy and chemotherapy. However, the potential effects of PBMT on pain control and analgesia resulting from these toxicities is still controversial. The aim of this systematic review was to compile available evidence of the effects of PMBT on pain control and reduced use of analgesics in HNC patients. We searched three indexed databases: MEDLINE/PubMed, Embase, and Scopus. The databases were reviewed up to and including December 2018. Only human clinical studies in English language were selected. Information was only available for mucositis and radiodermatitis. Fifteen out of 1112 studies met the inclusion criteria (14 for oral mucositis (OM) and 1 for radiodermatitis). From the 14 studies involving the prevention and treatment of OM, 10 had the study subjects compared to a placebo group. Of these 10 studies, all but 1 showed statistically significant difference related to pain control favoring the PBMT group. The study that compared PBMT with other treatment modality showed better results in pain control with PBMT. It appears that PBMT application frequency and potency impact on pain control. The only study involving the prevention and treatment of radiodermatitis was compared to placebo arm and showed statistically significant difference related to pain control favoring the PBMT group. Seven studies compared the need of analgesic medication between PBMT and placebo groups. Of these, five studies showed that the use of analgesic medication was significantly higher in the placebo group. The current evidence supports that PBMT is effective in pain control resulting from OM and radiodermatitis and may also reduce the need for analgesics. The evidence is not yet available of the effects of PBMT in other HNC treatment-related toxicities.

Tumor safety and side effects of photobiomodulation therapy used for prevention and management of cancer treatment toxicities. A systematic review.

Photobiomodulation therapy (PBMT), also known as low-level laser therapy (LLLT), has been increasingly used for the treatment of toxicities related to cancer treatment. One of the challenges for the universal acceptance of PBMT use in cancer patients is whether or not there is a potential for the light to stimulate the growth of residual malignant cells that evaded oncologic treatment, increasing the risk for tumor recurrences and development of a second primary tumor. Current science suggests promising effects of PBMT in the prevention and treatment of breast cancer-related lymphedema and oral mucositis, among other cancer treatment toxicities. Nevertheless, this seems to be the first systematic review to analyze the safety of the use of PBMT for the management of cancer-related toxicities. Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 27 articles met the search criteria. Selected studies included the use of PBMT for prevention and treatment of oral mucositis, lymphedema, radiodermatitis, and peripheral neuropathy. Most studies showed that no side effects were observed with the use of PBMT. The results of this systematic review, based on current literature, suggest that the use of PBMT in the prevention and management of cancer treatment toxicities does not lead to the development of tumor safety issues.

The performance of digital microscopy for primary diagnosis in human pathology: a systematic review.

Validation studies of whole slide imaging (WSI) systems produce evidence regarding digital microscopy (DM). This systematic review aimed to provide information about the performance of WSI devices by evaluating intraobserver agreement reported in previously published studies as the best evidence to elucidate whether DM is reliable for primary diagnostic purposes. In addition, this review delineates the reasons for the occurrence of discordant diagnoses. Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 13 articles were included. The total sample of 2145 had a majority of 695 (32.4%) cases from dermatopathology, followed by 200 (9.3%) cases from gastrointestinal pathology. Intraobserver agreements showed an excellent concordance, with values ranging from 87% to 98.3% (κ coefficient range 0.8-0.98). Ten studies (77%) reported a total of 128 disagreements. The remaining three studies (23%) did not report the exact number and nature of disagreements. Borderline/challenging cases were the most frequently reported reason for disagreements (53.8%). Six authors reported limitations of the equipment and/or limited image resolution as reasons for the discordant diagnoses. Within these articles, the reported pitfalls were as follows: difficulties in the identification of eosinophilic granular bodies in brain biopsies; eosinophils and nucleated red blood cells; and mitotic figures, nuclear details, and chromatin patterns in neuropathology specimens. The lack of image clarity was reported to be associated with difficulties in the identification of microorganisms (e.g., Candida albicans, Helicobacter pylori, and Giardia lamblia). However, authors stated that the intraobserver variances do not derive from technical limitations of WSI. A lack of clinical information was reported by four authors as a source for disagreements. Two studies (15.4%) reported poor quality of the biopsies, specifically small size of the biopsy material or inadequate routine laboratory processes as reasons for disagreements. One author (7.7%) indicated the lack of immunohistochemistry and special stains as a source for discordance. Furthermore, nine studies (69.2%) did not consider the performance of the digital method-limitations of the equipment, insufficient magnification/limited image resolution-as reasons for disagreements. To summarize the pitfalls of digital pathology practice and better address the root cause of the diagnostic discordance, we suggest a Categorization for Digital Pathology Discrepancies to be used in further validations studies. Among 99 discordances, only 37 (37.3%) had preferred diagnosis rendered by means of WSI. The risk of bias and applicability concerns were judged with the QUADAS-2. Two studies (15.4%) presented an unclear risk of bias in the sample selection domain and 2 (15.4%) presented a high risk of bias in the index test domain. Regarding applicability, all studies included were classified as a low concern in all domains. The included studies were optimally designed to validate WSI for general clinical use, providing evidence with confidence. In general, this systematic review showed a high concordance between diagnoses achieved by using WSI and conventional light microscope (CLM), summarizes difficulties related to specific findings of certain areas of pathology-including dermatopathology, pediatric pathology, neuropathology, and gastrointestinal pathology-and demonstrated that WSI can be used to render primary diagnoses in several subspecialties of human pathology.

Intravenous bisphosphonate therapy does not thicken cementum or change periodontal ligaments of cancer patients.

OBJECTIVE: To test the hypothesis that intravenous (IV) bisphosphonate (BP) therapy thickens or alters the micromorphology of cementum and periodontal ligament (PDL) in cancer patients. STUDY DESIGN: Thirty-two teeth extracted from 24 cancer patients and separated into test (patients who have undergone IV BP therapy, n = 16) and control (patients naive to BP therapy, n = 16) groups were studied. Cementum thickness was measured in 3 different areas of the dental root with polarized light microscopy. PDL was assessed by optical light microscopy and the immunohistochemical expression of periostin. RESULTS: No significant difference was detected in cementum thickness (apical, P = .06; medium, P = .16; cervical, P = .18) between groups. The numbers of fibroblasts in PDL (P = .56), incremental lines of cementum (P = .51) and the immunohistochemical patterns of periostin expression in PDL (P = .68) did not differ between groups. CONCLUSION: IV BP therapy does not thicken cementum or change the micromorphology of PDL.

Structural Analysis of Enamel in Teeth from Head-and-Neck Cancer Patients Who Underwent Radiotherapy.

OBJECTIVE: To analyze macroscopic, microscopic, and ultrastructural aspects of enamel from head-and-neck cancer patients submitted to radiotherapy. MATERIALS AND METHODS: Twenty sound extracted permanent molars were used and divided into 2 groups. The experimental group consisted of 10 molars from head-and-neck cancer patients submitted to radiotherapy with total doses that ranged from 50 to 70 Gy. Ten molars from patients who did not receive radiotherapy were matched with experimental-group samples by anatomic tooth group and comprised the control group. To perform a macroscopic analysis, standardized photos of different enamel faces were taken with a camera. Teeth were subjected to longitudinal cuts and hand polished to a final thickness of 0.1 mm. Enamel was analyzed under polarized light microscopy, and optical retardation values of birefringence were calculated in cervical, cusp, and occlusal pit areas. Subsequently, the same enamel areas were analyzed by scanning electron microscopy. Data from optical retardation values were statistically analyzed by 2-way ANOVA and Fisher's test (α < 0.05). RESULTS: No macroscopic differences were observed between the irradiated and control groups. Polarized light microscopy analysis revealed that cervical enamel exhibited darker areas characterized by discrete birefringence patterns compared to the control enamel. Optical retardation values were only significantly different in the cervical enamel of the irradiated and control groups (p < 0.0001). Scanning electron microscopy analysis revealed more evident interprismatic spaces in the cervical and outer cusp enamel of irradiated samples. CONCLUSIONS: Head-and-neck radiotherapy reduced optical retardation values of birefringence in cervical enamel, and the interprismatic spaces became more evident.