Positive Oral Squamous Cell Carcinoma Research Articles

Triple Positive Oral Squamous Cell Carcinoma Patients Predict Poor Survival Outcomes: Multiple Factor Positivity Warrants the Need for Modified Treatment Approaches

Triple Positive Oral Squamous Cell Carcinoma Patients Predict Poor Survival Outcomes: Multiple Factor Positivity Warrants the Need for Modified Treatment Approaches

148 Predictors and outcomes of Contralateral Lymph node involvement in node positive oral squamous cell carcinoma: A retrospective analysis of 180 patients.

148 Predictors and outcomes of Contralateral Lymph node involvement in node positive oral squamous cell carcinoma: A retrospective analysis of 180 patients.

HPV and p16 expression association with 5-year survival in oral squamous cell carcinoma patients of north-east India

BackgroundIn our study, we examined the 5-year survival of OSCC patients with HPV positive or negative status along with p16 protein expression. MethodA total of 72 biopsy tissue specimens from histologically confirmed oral squamous cell carcinoma (OSCC) patients were collected. HPV detection and genotyping were performed using HPV E6/E7 and HPV- type-specific multiplex primer for nested-PCR. Immunohistochemistry evaluation of pl6 was conducted. SPSS statistical software (ver 20) was used for data analysis. ResultsHigh risk-HPV (hr-HPV) DNA positivity was found in 27.7% (n = 20) of OSCC patients. Stage III OSCC patients were 7.80 times more likely to survive 5 years than stage IV patients (OR-7.80 CI-95%; P-0.03). Among the hr-HPV positive OSCC patients, we found that the median survival time for the 1st year (95%), 3 years (78.5%), and 5 years (38.5%) was significantly higher than that of the hr-HPV negative [1st year (78.6%), 3 years (45.2%) and 5 years (38.5%)] OSCC patients (P-0.03 The survival of male patients with hr-HPV positive OSCC is 9.75 times greater than the survival of patients with HPV negative OSCC (OR-9.75; CI-95%; P-0.05). The p16 expression level (low to overexpression) group and negative P16 expression group of OSCC patients have not demonstrated a significant association with 5-year survival. ConclusionWe conclude that in OSCC cases of North-East India, the presence of hr-HPV in OSCC cases could be a good predictor of 5-year survival rate. Expression of p16 does not appear to have any significant association with 5-year survival.

Expression of p53 in toluidine blue positive oral squamous cell carcinoma lesions and expression of Ki67 in vinegar positive oral squamous cell carcinoma lesions.

The aims of this study were to investigate the sensitivity and specificity of toluidine blue and/or vinegar in oral cancer screening and to examine the correlation between clinical screening using toluidine blue and vinegar and the expression of the tumor marker p53 and proliferation marker Ki67, respectively. The study consisted of 87 patients with suspected oral squamous cell carcinoma lesions. Toluidine blue and/or vinegar were applied to the lesions, followed by biopsies. The tissues were diagnosed histopathologically and underwent immunohistochemical process for p53 or Ki67. The results revealed that the sensitivity and specificity of oral cancer screening using toluidine blue were 93% and 46%, respectively; whereas the sensitivity and specificity using vinegar were 85% and 81%, respectively. A statistically significant correlation between the use of vinegar and the expression of Ki67 (p = 0.019) was observed. Although there was a difference in the expression of p53 between specimens that were positive and negative to toluidine blue, the correlation did not reach a significant level. Based on the results from this study, vinegar has a lower sensitivity than toluidine blue but a higher specificity for oral cancer screening. The results of the clinical screening using vinegar correlated with the expression of Ki67 at the cellular level.

HPV infection in oral cancer, our experience: prevalence, clinical implications, and current vaccination program in Spain.

Oral cancer is the 11th most common type of cancer in the world, with established major risk factors as tobacco and alcohol, and recently included high-risk human papillomavirus types 16 and 18. HPV types 16 and 18 are the etiologic agents of cervical cancers and a proportion of oropharyngeal cancers. However, the picture of HPV and the clinical implications of oral cancers are not clear with most reports combining oral cancer data with head and neck cancers. It has been confirmed as a favorable prognostic factor in oropharyngeal cancer. However, the prognostic value of HPV in oral squamous cell carcinoma is still unclear. The main objective of this article is to present the evidence encountered following a bibliographical review of recent publications specifically related to oral cancer and its differences from oropharyngeal cancer. The secondary goals are to present the findings of a five-year retrospective observational study of the prevalence of HPV infection in oral cancer patients treated by the Oral and Maxillofacial Surgery Department at La Paz University Hospital (Madrid, Spain), and finally, we to evaluate and compare our country's HPV prevention program in comparison to other European countries. According to the review of the literature, HPV positive oral squamous cell carcinoma is associated with significantly decreased overall survival and distant control. Bibliographic review suggest HPV infection can be used as a negative prognostic factor in oral squamous cell carcinoma. As regards diagnostic testing for HPV, it should be extended to as many cases of oral cavity squamous cell carcinoma as possible, especially in those with risk factors. The current vaccination program in Spain does not have adequate coverage and is significantly under the level of other European Union countries; it should be expanded and catch-up strategies should be included. Key words:HPV, OSSC, Papillomavirus, oral carcinoma, prevention.

Immunohistochemical evaluation of tumor angiogenesis and architectural changes in regional lymph nodes of oral squamous cell carcinoma (OSCC)

Aim: To evaluate the mean vascular area (MVA) and to correlate it with immunomorphological pattern of lymph nodes. Materials and Methods: A total of 50 positive OSCC cases (clinically and histopathologically diagnosed) from Santosh Medical College and I.T.S Dental college, ghaziabad were taken for the study. The lymph nodes collected were stained with routine hematoxylin & eosin and accessed for immunomorphological pattern. The sections were evaluated immunohistochemically by anti-von Willebrand factor (vWF) VIII to analyze the micro vessels in OSCC. Results: Three hundred and forty two lymph nodes were evaluated and the most predominant lymph node patterns were found to be Germinal Center Predominance (37.43%). Our results showed a significant association between tumor node metastasis (TNM) staging, histopathological grading, and mean vascular area with lymph node reactivity pattern. Conclusion: There was an increase in angiogenesis with in different grades of OSCC and mean vascular area with morphological pattern of lymph nodes can be used as an additional parameter which would help in assessing prognosis and survival of the patient.

Oncological safety of harvesting local flaps from the neck in clinically node positive patients with oral squamous cell carcinoma.

e18065 Background: Reconstruction of complex orofacial defects following tumour resection has always posed as a challenge for clinicians for providing functional and morphological outcomes. Though microvascular free flaps revolutionized reconstruction, local flaps provide a viable alternative in resource constraint settings. Oncological safety of harvesting local flaps has always been a matter of debate in oral squamous cell carcinoma due to proximity of nodal stations. Available literature on oncological safety is limited to clinically node negative patients. The purpose of this study was to evaluate the oncologic safety of local flaps in clinically node positive patients. Methods: Retrospective analysis of data available of all patients diagnosed with clinically node positive oral squamous cell carcinoma who underwent modified radical neck dissection at Malabar Cancer Centre during the period January 2012 to December 2017 was done. Demographic profile, tumour characteristics and pathological outcomes were compiled. The factors included were pathological tumour, nodal stage, levels of nodes involved, extranodal extension, choice of flap and site of recurrence. Fisher's exact test was used to compare recurrence patterns between local and regional flaps. Results: A total of 309 clinically node positive patients were analyzed with a median follow up of 4 years. Overall incidence of pathologically proven nodal metastases to ipsilateral levels Ia Ib, II, III, IV and V were 8.1%, 35.3%, 39.5%,15.5%, 2.9% and 1.3% respectively. Level Ia was most commonly involved in buccal mucosa and tongue cancers. Levels Ib, II, III were most commonly involved in tongue and buccal mucosa cancers. Level IV was commonly involved in tongue cancers while level V in cancer of retromolar trigone. Local flaps analyzed were submental flap (2.6%), supraclavicular flap (2.6%), infrahyoid flap (2.6%), sternocleidomastoid muscle flap (4.5%), nasolabial flap (1.3%), facial artery myomucosal flap (1.6%). Pathological nodal positivity was 60% and 52% in local and regional flaps respectively. Amongst the patients who had reconstruction with submental flap there were no nodal recurrences at level Ia, only 1 patient had recurrence at flap site. Amongst the patients who had reconstruction with supraclavicular flap there was 1 patient with pathological involvement of level V as per histopathological report but no nodal recurrences at level V. There was no difference in pattern of nodal recurrence between local and regional flaps (p = 0.436). Conclusions: This retrospective analysis is the first of its kind analysing the oncological safety of harvesting local flaps in clinically node positive oral squamous cell carcinoma. Thus, with appropriate management of the levels Ia and V nodal compartment, oncologic outcomes are not compromised, thereby making it oncologically sound to harvest local flaps in N+ neck.

Peri-tumoral infiltrate associates with postoperative prognosis of patients with OSCC: Stronger association in HPV negative patients

PurposeThe current data on the relationship between local inflammatory infiltration and prognosis in oral squamous cell carcinoma (OSCC) are limited and controversial, especially in different HPV status. In this study, we analyzed the relationship between peri-tumoral inflammatory infiltrate (PTI) and HPV status and prognosis of patients with OSCC after surgery. MethodsA retrospective cohort of 99 primary OSCC patients who underwent surgery was constructed. P16 immunohistochemistry was used to determine HPV status. PTI was determined by hematoxylin-eosin staining and quantified into four levels: none (Score 0), weak (Score 1), moderate (Score 2) and strong (Score 3). The associations of PTI with clinico-pathological characteristics, HPV status and survival were examined. ResultsMost OSCC patients had weak to moderate PTI. PTI was significantly associated with lymph node metastasis (P = 0.041), and patients with moderate PTI had significantly better OS (P = 0.009) than those with no PTI. In HPV negative OSCC, patients with moderate PTI also had significantly better OS (P = 0.019) than those with no PTI. However, PTI was not significantly associated with survival in HPV positive OSCC. ConclusionsIn HPV negative OSCC, moderate PTI may suggest a better postoperative prognosis than no PTI.

Demographic Profile of p16 Immunopositive and HPV DNA PCR Positive Oral Squamous Cell Carcinoma in a Large Cohort of Indian Patients.

Background:The Indian subcontinent has the highest incidence of oral cavity squamous cell carcinoma in the world. The high incidence of tobacco chewing habit with or without smoking has been found to be the chief culprit. However in a minor subset of patients Human Papilloma Virus may play a role. Materials and Methods:A total of 800 cases of Oral squamous cell carcinoma were included in the study. The patients were given a questionnaire comprising of questions about demographic details and habits. The biopsy samples were routinely processed for immunohistochemistry for p16 (E6H4 clone, CINtec histology, Roche diagnostics). Cases with 2+/3+ positive nuclear staining with more than 75% cells immunopositive were taken as p16 immunopositive as per the AJCC criteria and were further subjected to HPV DNA PCR for which DNA was extracted from the formalin fixed paraffin embedded tissue. Results: Out of 800 OSCC cases 139 (17.37%) showed p16 immunopositivity by AJCC criteria. Out of these, 104 (104/139, 74.8%) cases were positive by HPV DNA PCR for HPV-16/18. Following patient characteristics were associated with a higher proportion of p16 and HPV DNA positivity–urban residence, vegetarian diet, illiteracy, graduate or higher education. No correlation was noted with gender, tobacco smoking or chewing habits, religion, occupation or site of tumor. The p16 immunopositivity was higher in the younger age group with no tobacco habits. Conclusion:A significant proportion of OSCC cases in India are associated with HPV infection. A higher percentage of p16 immunopositivity amongst younger patients with no tobacco habits points towards a distinct subset of patients in whom HPV may be the chief culprit and not just playing a supporting role.

Immunohistochemical study of epidermal growth factor receptor, human epidermal growth factor receptor 2/neu, p53, and Ki67 in oral squamous cell carcinoma.

Introduction:Oral squamous cell carcinoma (OSCC) is the most common malignant tumor occurring in the oral cavity.Aim:The present study was conducted to evaluate the biomarkers such as epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2/neu), p53 and Ki67 expression in OSCC cases, and its correlation with other well-established clinicopathological parameters.Materials and Methods:Seventy cases of OSCC cases diagnosed between 2015 and 2019 were included in the study. A technique of manual tissue microarray was employed for the analysis of expression of IHC markers such as EGFR, HER2/neu, p53, and Ki67 in all cases. Results were subjected to the statistical analysis.Results:A statistically significant positive association was noted between EGFR expression and tumor grade, tumor stage, and p53 immunoexpression in OSCC cases. Increased EGFR expression was noted insignificantly in OSCC cases with lymph node (LN) metastasis and Ki67 positive cases. Statistically significant positive association was noted between HER2/neu expression and tumor grade and stage of oral SCC cases. Increased HER2/neu expression was noted insignificantly in OSCC cases with LN metastasis, p53 and Ki67 positive OSCC cases. A statistically significant positive association was noted between percent of tumor cells expressing EGFR, HER2/neu, p53 and Ki67, and grade of OSCC.Conclusion:This study intends to document prognostic utility of EGFR and HER2/neu expression in OSCC cases in the Indian setting and contribute to the data pool which could aid in formulating individual tailored therapy that includes targeted therapy in oral SCC cases.

CD68+ Macrophage Infiltration Associates With Poor Outcome of HPV Negative Oral Squamous Carcinoma Patients Receiving Radiation: Poly(I:C) Enhances Radiosensitivity of CAL-27 Cells but Promotes Macrophage Recruitment Through HMGB1.

Patients with human papillomavirus (HPV) negative oral squamous cell carcinoma (OSCC) generally have poor clinical outcomes and worse responses to radiotherapy. It is urgent to explore the underlining mechanisms of the distinct prognoses between HPV negative and HPV positive OSCC and to develop effective therapy strategy to increase the survival rate of HPV negative OSCC patients. We conducted a retrospective cohort of 99 resected OSCC patients to evaluate the prognosis of HPV negative and HPV positive OSCC patients receiving radiation or not. We further addressed the association of CD68+ macrophage infiltration with HPV status and the effects on survival of OSCC patients. We also used the TCGA-OSCC cohort for further verification. Based on the cohort study, we applied a synthetic dsRNA polymer, polyriboinosinic-polyribocytidylic acid (poly(I:C)), on CAL-27 (HPV negative OSCC cells). We co-cultured its condition medium with THP-1 derived macrophage and examined the cytokines and macrophage migration. We found that high CD68+ macrophage infiltration associated with poor overall survival in HPV negative OSCC patients receiving radiation. In vitro, poly(I:C) could induce apoptosis and enhance the radiosensitivity, but increase macrophage recruitment. Targeting HMGB1 could inhibit IL-6 induction and macrophage recruitment. Our findings indicated that CD68+ macrophage might play an important role in the outcomes of HPV negative OSCC patients receiving radiation. Our findings also suggested that radiation combined poly(I:C) might be a potential therapy strategy to increase the radiation response and prognosis of HPV negative OSCC. Notably, HMGB1 should be targeted to inhibit macrophage recruitment and enhance overall therapy effects.

RETRACTED ARTICLE: Interplay between cancer cells and M2 macrophages is necessary for miR-550a-3-5p down-regulation-mediated HPV-positive OSCC progression

BackgroundHuman papillomavirus (HPV)-positive oral squamous cell carcinoma (OSCC) is increasing worldwide with typically higher grade and stage, while better prognosis. microRNAs (miRNAs) has been shown to play a critical role in cancer, however, their role in HPV-positive OSCC progression remains unclear.MethodsmiRNA microarray was performed to identify differentially expressed miRNAs. qRT-PCR and FISH were performed to determine the relative expression of miR-550a-3-5p. CCK-8, Flow cytometry, Wound healing, Cell invasion assays and xenograft experiments were conducted to analyze the biological roles of miR-550a-3-5p. Tumor-associated macrophages (TAMs) generation, co-culturing of cancer cells with TAMs, Western blot, Dual-luciferase reporter gene assay, Immunohistochemistry and animal studies were performed to explore the mechanisms underlying the functions of miR-550a-3-5p.ResultsWe identified 19 miRNAs differentially expressed in HPV-positive OSCC specimens and miR-550a-3-5p was down-regulated. The low expression of miR-550a-3-5p correlated with higher tumor size and nodal metastasis of HPV-positive OSCC patients. Then, we found that miR-550a-3-5p suppressed the migration, invasion and EMT of HPV-positive OSCC cells dependent on decreasing M2 macrophages polarization. Moreover, miR-550a-3-5p, down-regulated by E6 oncoprotein, inhibited M2 macrophages polarization by YAP/CCL2 signaling, which in turn abrogating EMT program in HPV-positive OSCC cells. In addition, in both xenografts and clinical HPV-positive OSCC samples, miR-550a-3-5p levels were inversely associated with YAP, CCL2 expressions and the number of M2 macrophages.ConclusionsE6/miR-550a-3-5p/YAP/CCL2 signaling induces M2 macrophages polarization to enhance EMT and progression, revealing a novel crosstalk between cancer cells and immune cells in HPV-positive OSCC microenvironment.

Nuclear Magnetic Resonance Metabolomics Biomarkers for Identifying High Risk Patients with Extranodal Extension in Oral Squamous Cell Carcinoma.

Extranodal extension (ENE) is an independent adverse prognostic factor in oral squamous cell carcinoma (OSCC), and is difficult to identify preoperatively. We aimed to discover biomarkers for high risk patients with ENE. Tandem tissue, plasma, and urine samples of 110 patients with OSCC were investigated through 600-MHz nuclear magnetic resonance (NMR) metabolomics analysis. We found that the levels of creatine, creatine phosphate, glycine, and tyramine in plasma significantly decreased in stage IV ENE positive OSCC compared with stage IV ENE negative OSCC. To understand the underlying mechanism behind the alteration of plasma metabolites, our tissue analysis revealed that the carnitine level significantly increased in tumors but significantly decreased in the adjacent normal tissue in advanced stage OSCC, in addition to decreased levels of alanine and pyruvate in tumor tissues. The global metabolomics analysis on tumor tissues also showed that stage IV tumors with an ENE positive status demonstrated higher levels of aspartate, butyrate, carnitine, glutamate, glutathione, glycine, glycolate, guanosine, and sucrose but lower levels of alanine, choline, glucose, isoleucine, lactate, leucine, myo-inositol, O-acetylcholine, oxypurinol, phenylalanine, pyruvate, succinate, tyrosine, valine, and xanthine than tumors with an ENE negative status. We concluded that metabolomics alterations in tumor tissues correspond to an increase in the tumor stage and are detectable in plasma samples. Metabolomic alterations of OSCC can serve as potential diagnostic markers and predictors of ENE in patients with stage IV OSCC.

MET ectodomain shedding is associated with poor disease-free survival of patients diagnosed with oral squamous cell carcinoma.

Ectodomain shedding unleashes the aggressive nature of the MET oncogene product. Using specific C- and N-terminal MET antibodies (D1C2 and A2H2-3), MET protein status (i.e., no MET, decoy MET, transmembranous C-terminal MET with or without the ectodomain) was investigated in oral squamous cell carcinoma. For the cancers showing transmembranous C-terminal MET, the impact of ectodomain shedding on prognosis was investigated. To examine ectodomain shedding, reduced lysates of oral squamous cell carcinoma cell lines were immunoblotted using D1C2 and an ELISA was performed on culture media using A2H2-3. In addition, reduced lysates of fresh frozen tissues of 30 oral squamous cell carcinoma were immunoblotted using D1C2 and immunohistochemistry was performed on corresponding formalin-fixed paraffin-embedded tissues using both antibodies on parallel sections. To examine MET protein status, differences between membranous D1C2 and A2H2-3 immunoreactivities were scored using parallel tissue microarray sections representing 156 oral squamous cell carcinoma. The prognostic value of ectodomain shedding was examined using Cox regression analysis for disease-free survival and overall survival. Ectodomain shedding was observed in all cell lines, 43% (n = 13) of fresh frozen and 50% (n = 15) of formalin-fixed paraffin-embedded cancers (27% overlap, n = 8). The tissue microarray showed no MET in 23% (n = 36), decoy MET in 9% (n = 14), and transmembranous C-terminal MET in 68% (n = 106) of examined cancers. Within the latter group, ectodomain shedding occurs in 36% (n = 38) of the cases and is independently associated with poor disease-free survival (HR = 2.41; 95% CI, 1.35-4.30 and P = 0.003)-though not overall survival (HR = 1.64; 95% CI, 0.92-2.94 and P = 0.095)-after correcting for factors known to influence survival. In conclusion, MET ectodomain shedding occurs in transmembranous C-terminal MET positive oral squamous cell carcinoma and is independently associated with disease-free survival. These findings might aid in designing companion diagnostics for targeted therapies directed against MET.

Salivary proteins from dysplastic leukoplakia and oral squamous cell carcinoma and their potential for early detection

Dysplastic leukoplakia (LP) of the oral cavity is a potentially malignant condition for oral squamous cell carcinoma (OSCC), early detection of which remains an unmet clinical need. In an effort to develop non-invasive biomarker based method for early detection of the disease, differential proteomic profiling was carried out with the saliva from patients with risk habits and diagnosed with LP and those with lymph node negative and positive OSCC in comparison to healthy controls with risk habits. Ninety three proteins were observed at elevated level (≥1.5 fold), and 30 were prioritized based on a scoring system comprising of confidence of identification, presence in the various specimen groups, functional relevance, and their secretory potential. Verification was carried out in independent patient cohorts for 8 selected, representative, upregulated proteins using ELISA. Three of them CD44, S100A7, and S100P were significantly altered in patients with LP as well as OSCC and can be regarded as a panel of biomarker candidates for early detection of the malignancy. Other members may also be investigated in a targeted manner to expand the portfolio of biomarkers for early detection. The mass spectrometry data are available via ProteomeXchange with identifier PXD015722. SignificanceThere is an unmet clinical need for non-invasive, biomarker based methods for the improved early detection and the subsequent management of oral cancer. The study represents differential proteome profiling of the saliva of patients with oral dysplastic leukoplakia (LP) – a potentially malignant lesion, patients diagnosed with oral squamous cell carcinoma (OSCC), and healthy controls to identify potential markers for the purpose of early detection of malignancy. From among the matched and prioritized proteins with elevated levels in the saliva of patients with LP and those with OSCC, eight were verified. Three of them – CD44, S100A7 and S100P appeared promising candidates as biomarkers for early detection of the neoplastic predisposition and may form the basis of clinical assays for this purpose.

ASSOCIATION OF HIGH RISK HUMAN PAPILLOMA VIRUS (HPV-16/18) WITH P16 PROTEIN IN ORAL PREMALIGNANT LESIONS AND ORAL SQUAMOUS CELL CARCINOMA

Background: Oral cancer is a major problem globally. The strong causal association with tobacco, prevalent in Pakistan makes it imperative to know the role of molecular events in oral oncogenesis. We aim to evaluate high risk HPV 16/18 and p16 in oral premalignant lesions (OPL) and oral squamous cell carcinoma (OSCC). We further analyze the association between high risk human papilloma virus (HR-HPV16/18) and p16 in OPL and OSCC. Methods: A total of 100 OSCC and 50 OPL cases were included. Demographic data along with habitual exposure to smoked and chewable tobacco, betel and gutka etc., was noted. We evaluated p16 in OPL and OSCC by immunohistochemistry, HPV was detected by polymerase chain reaction. Data was entered and analyzed using SPSS 21. Chi square and Fisher exact were applied to determine the association of HPV and p16 with different variables. Results: Out of 50 OPL, 14% were positive and 86% were negative for p16 whereas out of 100 OSCC, 18% were positive and 82% were negative. Out of 50 OPL, HPV was detected in 6% whereas out of 100 OSCC, 15% were positive. Highly significant co expression of HPV with p16 was observed in all 15 (100%) HPV positive OSCC cases (p = 0.001). However, 3 out of 18 cases, which showed p16 expression, did not show HPV infection. Conclusion: Role of p16 as a surrogate marker for HPV in OSCC can be supported in the present study. Moreover a Chemical carcinogen like tobacco is considered as major associative risk factor with p16 and HPV in concert.

Prognostic implications of the 8th edition American Joint Committee on Cancer (AJCC) staging system in oral cavity squamous cell carcinoma

BackgroundThe American Joint Committee on Cancer (AJCC) has changed the staging system of oral squamous cell carcinoma (OSCC) in the 8th edition of its staging manual to include depth of invasion (DOI) of the primary tumor as a modifier to the T category and extranodal extension (ENE) to upstage node positive OSCC. This study aims to evaluate the performance of the AJCC 8 pathologic staging system in OSCC and compare it to its predecessor (AJCC 7). MethodsAnalysis of 663 patients with OSCC from a prospective database was performed using the Cox proportional hazards competing risk model. The prognostic performance of the pathologic staging system was assessed using the Akaike Information Criterion (AIC) and Harrell’s concordance index (C-index). ResultsAJCC 8 led to upstaging of 35.6% (N = 235) of patients in this cohort. Both AJCC 7 and 8 show limited monotonicity and poor stratification between stage groups I to III. The estimates for model performance reveal that AJCC 8 has modest predictive capacity for overall survival (OS) and disease specific survival (DSS) (Harrell’s C of 0.70 and 0.74, respectively) but is superior to AJCC 7 (Harrell’s C of 0.65 and 0.69, respectively). ConclusionsThe AJCC 8 staging system is more complex than its former version due to the inclusion of DOI and ENE. Compared with AJCC 7, it performs better in stratifying survival of OSCC patients by stage.

HPV knowledge gaps and information seeking by oral cancer patients

ObjectivesThe incidence of human papillomavirus (HPV) positive oral squamous cell carcinoma (OSCC) continues to increase over time, challenging healthcare providers to address their patients’ HPV-related concerns. Materials and methodsThis prospective study assessed health literacy, HPV knowledge, utilization and trust in information sources among patients with incident HPV-positive or HPV-negative OSCC diagnosed at the Ohio State University from 2011 to 2015. Health literacy was assessed with a standardized scale. Additional questions evaluated HPV knowledge (including transmission, prevalence, health consequences and treatment), the frequency and type of information sources sought, and trust in those sources. ResultsSurveys were collected from 372 OSCC cases (HPV-positive, n=188; HPV-negative, n=184). Despite high mean health literacy scores, only 45.2% of HPV-related knowledge questions were answered correctly. HPV was known to be a sexually transmitted infection and a cause of cervical and anal cancer by 66.0%, 56.5% and 15.2%, respectively. In all domains, cases with HPV-positive OSCC were significantly more informed than HPV-negative cases (for all, p<0.01). Only 52.7% and 56.2% of patients with HPV-positive OSCC felt they knew enough to be comfortable discussing HPV with their doctor or sexual partner, respectively. The most frequently used information source was the internet (80.9%), which ranked 8th in trust of 15 possible sources. Although most (95.5%) patients trusted information from their doctors, only 37.9% used doctors as an information source. ConclusionsDoctors are a highly trusted, but infrequent utilized, information source and should facilitate patient access to high-quality HPV information sources.

Expression of TIMP-2 in HPV-16 infected oral squamous cell carcinoma in patients in Iraq

Aim: To determine the expression of tissue inhibitors of metalloproteinases (TIMP-2) in oral squamous cell carcinoma (OSCC) and the difference in its expression level between positive and negative HPV-16 (human papilloma virus- 16) OSCC patients. Methods: This study was conducted on 33 biopsies obtained from patients with OSCC and 10 normal oral mucosa as controls. In situ hybridization (ISH) was used to investigate the presence of HPV-16, while immunohistochemistry (IHC) was used to estimate the expression level of TIMP-2. Results: The TIMP-2 was expressed in 27 (81.8%) of OSCC sections with no significant difference between its expression level in HPV-16 positive and HPV-16 negative OSCC cases (p=0.058). TIMP-2 was found to be highly expressed in OSCC sections, and the presence of HPV was not related to its overexpression. Conclusions: The percentage of samples that appeared to accommodate detectable HPV-16 was high, but no significant difference was observed in relation to TIMP-2 expression level. Future studies with a larger number of patients are highly recommended to address the possible association between TIMp-2 and OSCC positive HPV-16.

Estrogen and Progesterone hormone receptor expression in oral cavity cancer.

BackgroundRecent studies have shown an increase in the incidence of oral squamous cell carcinoma (OSCC) in younger patients. The hypothesis that tumors could be hormonally induced during pregnancy or in young female patients without the well-known risk factors alcohol or tobacco abuse seems to be plausible.Material and MethodsEstrogen Receptor alpha (ERα) and Progesterone Receptor (PR) expression were analyzed in normal oral mucosa (n=5), oral precursor lesions (simple hyperplasia, n=11; squamous intraepithelial neoplasia, SIN I-III, n=35), and OSCC specimen. OSCCs were stratified in a young female (n=7) study cohort and older patients (n=46). In the young female study cohort three patients (n=3/7) developed OSCC during or shortly after pregnancy. Breast cancer tissues were used as positive control for ERα and PR expression.ResultsERα expression was found in four oral precursor lesions (squamous intraepithelial neoplasia, SIN I-III, n=4/35, 11%) and in five OSCC specimen (n=5/46, 11%). The five ERα positive OSCC samples were older male patients. All patients within the young female study cohort were negatively stained for both ERα and PR.ConclusionsER expression could be regarded as a seldom risk factor for OSCC. PR expression seems to be not relevant for the development of OSCC. Key words:Oral squamous cell carcinoma, estrogen receptor, progesterone receptor, hormone receptor.