Prevalence and clinical implications of the HPV16 infection in oral cancer in Montenegro - Evidence to support the immunization program.

Oral squamous cell carcinoma (OSCC) makes 85-95% of all malignances in the oral cavity. Increasing evidence shows that the Human Papillomaviruses (HPVs) are preferentially associated with some oropharyngeal and OSCCs, namely the genotype 16. The aim of the present study was to determine the prevalence and clinical implications of HPV16 infection in oral squamous cell carcinoma in population of Montenegro.This study included 60 patients with OSCC (localized on the lower lip, tongue or/and floor of the mouth), surgically treated at the Clinical Centre of Montenegro from 2012 to 2018. Surgically obtained formalin-fixed and paraffin-embedded specimens were used for histopathological analysis and HPV16 genome detection using standard Polymerase Chain Reaction (primers for detection of E6 gene). Each individual was further followed up for the period of three years and for different clinico-pathological characteristics, including disease free interval (DFI).The prevalence of HPV16 infection in OSCCs was 23.3% and the infection was significantly more common in female patients (P = 0.038). No significant correlation was detectable between HPV16 infection and the patients' age (P = 0.302), tumor site (P = 0.125), tumor grade (P = 0.363) and disease stage (P = 0.995). Observing the total sample the DFI was not significantly different for HPV16-positive versus HPV16-negative patients (P = 0.427), but a gender-based difference in DFI was observed, with the significantly shorter DFI (Log Rank test, P = 0.003) in HPV16 positive female patients compared to male patients (P = 0.003).The results obtained in this study provide scientific evidence for the development of national HPV vaccination program in Montenegro.

Distribution of vaccine-related high-risk human papillomaviruses and their impact on the development of cervical dysplasia in women in Montenegro.

Cervical cancer (CC) is the third leading cause of death in women in Montenegro. Human papillomavirus (HPV) is the causative agent of CC however, HPV genotype distribution varies across regions. This study examined the distribution and impact of vaccine-related high-risk (HR)-HPVs on the development of cervical dysplasia in Montenegrin women. A total of 187 women who had a clinical indication for cervical biopsy were enrolled. Based on histopathological findings, women were classified into 2 groups, with and without dysplasia. HR-HPV was detected by real-time PCR. Twelve HR-HPV genotypes were detected in 40.6% of cervical samples. The 7 most prevalent HR-HPVs in order of decreasing frequency were HPV 16 (39.5%), 45 (23.7%), 31 (21.0%), 33 (17.1%), 18 (6.6%), 52 (6.6%), and 58 (6.6%), all of them are targeted by nonavalent vaccine. Vaccine-related HR-HPVs had a higher prevalence (92.1%) than the other HR-HPVs detected in HR-HPV-positive samples. Among HR-HPV-positive women, HPV 16 and 33 were more common in women with dysplasia than in those without dysplasia (HPV 16: 28.9 vs 7.2%; HPV 33: 11.8 vs 3.6%). HPV 16 was the most common HR-HPV genotype in cervical samples, followed by HPV 45, 31, 33, 18, 52, and 58. HPV 16 and 33 were shown to be associated with the development of cervical dysplasia. These results indicate that prophylactic nonavalent vaccine can potentially prevent approximately 90% of HR-HPV infections and 60% of cervical dysplasia cases in Montenegrin women.

Medication-Related Osteonecrosis of the Jaws: Two Center Retrospective Cohort Studies.

This retrospective cohort study aims to describe characteristics of patients with MRONJ, to identify factors associated with MRONJ development, and to examine variables associated with favourable outcome. Totally 32 patients were followed and observed: 21 females and 11 males, in the age range 35-84 in the period from 2009 to 2018. Clinical, radiological examination (Orthopantomograph and CBCT) and biopsy were performed in order to achieve diagnosis. Demographic and clinical variables were taken into consideration: sex, age, primary disease, medication type, mode of delivery, anatomic location, drug treatment duration, timing of tooth extraction, chemotherapy, presence of bone metastasis, aetiology of MRONJ, disease stage, and treatment modality. MRONJ developed under osteoporosis and malignant disease in 11 and 21 patients, respectively. MRONJ development was triggered by tooth extraction or trauma in 30 out of 32 cases, whereas the two patients developed MRONJ spontaneously. Stages I, II, and III were confirmed in 5 (16%), 18 (58%), and 9 (28%) patients, respectively. Mandible was affected in 23 (72%) patients. MRONJ was treated in our department by conservative and surgical modality. In this study we found that 65% of all patients were classified in the cured/improvement group and 35% in the stable/progression group. The female gender, osteoporosis as primary disease, oral regime intake, shorter period on BPs, earlier stage of disease, and specific anatomic localisation (frontal and premolar maxilla) were factors associated with better response to therapy and favourable clinical outcome. Comprehensive treatment protocol and further randomized studies are necessary for further improvements.

The third molars for indicating legal adult age in Montenegro.

AIM: From a medico-legal and penalty point of view, it is essential to conclude if an individual is a minor or an adult (18 years of age). Methods based on the third molar development have been used for this purpose. The present article aims to verify the Nolla's stages of mineralization of the third molars and a third molar maturity index (I3M) which is based on the measures of the projections of open apices normalized by their height in the sample of Montenegrins. METHOD AND SAMPLE: The sample consisted of 683 panoramic radiographs (324 males and 359 females) between 13 and 24 years of age. The specific mineralization stages of Nolla and the cut-off value of I3M < 0.08 was used to discriminate adults and minors. RESULTS: The best performance in discriminating adults and minors was for I3M < 0.08 followed by the Nolla stage 9. For I3M < 0.08 the results demonstrated high sensitivity of 0.92 and 0.82 and specificity of 0.94 and 0.96 in males and females, respectively. The proportions of correctly classified individuals were 0.93 in males and 0.89 in females. The Nolla stage 9 demonstrated the sensitivity of 0.95 and 0.85 and the specificity of 0.84 and 0.90 in males and females, respectively. The proportions of correctly classified individuals were 0.90 in males and 0.87 in females. CONCLUSION: The suggested value of I3M < 0.08 followed by Nolla stage 9 can be used to discriminate adults from minors with high specificity.

The role of TERT-CLPTM1L SNPs, hTERT expression and telomere length in the pathogenesis of oral squamous cell carcinoma.

The aim of this study was to assess TERT-CLPTM1L single-nucleotide polymorphisms (SNPs) (rs402710 C/T in the CLPTM1L gene; rs2736100 A/C and rs2736098 G/A in the TERT gene) as risk factors for development of oral squamous cell carcinoma (OSCC), and to investigate the relationship between the analyzed polymorphisms, relative telomere length (RTL), telomerase expression and clinicopathologic characteristics of OSCC in a Serbian population. Paraffin-embedded tumor samples and buccal swabs from cancer-free controls were genotyped using PCR-RFLP, while tumor RTL values and telomerase expression were estimated by real-time PCR and immunohistochemistry, respectively. CLPTM1L rs402710 and TERT rs2736100 polymorphisms were associated with a significantly increased risk of OSCC, and TERT rs2736098 with a significantly decreased risk. No significant association was found between TERT-CLPTM1L polymorphisms, tumor RTL values, telomerase expression, and clinicopathologic features, although a trend towards longer telomeres was evident in telomerase-positive samples and less advanced tumors. Kaplan-Meier survival analysis showed that patients with longer telomeres in their tumors had significantly better overall survival than patients with shorter telomeres. Our research seems to provide strong evidence for an association between CLPTM1L rs402710C/T and TERT rs2736100A/C SNPs and the risk of OSSC, and suggests that higher tumor RTL values and positive hTERT expression may be applicable as early prognostic markers.(J Oral Sci 58, 449-458, 2016).

Malignant ameloblastoma metastasis to the neck--radiological and pathohistological dilemma.

INTRODUCTION: Ameloblastomas are odontogenic epithelial, locally invasive tumors of slow growth and mostly of benign behavior. Their frequency is low (they account for 1% of all head and neck tumors and about 11% of tumors of dental origin). Malignant variations of ameloblastoma are malignant ameloblastoma and ameloblastic carcinoma. They constitute less than 1% of all ameloblastomas. We presented a case of malignant ameloblastoma of the mandible with neck metastasis. CASE REPORT: A patient, aged 72, presented with the following symptoms: pain in the lower jaw, swelling in the left submandibular area and difficult mouth opening. The patient was admitted to the Department of Oral and Maxillofacial Surgery, Clinical Center of Montenegro, two months after he had noticed the symptoms. Panoramic radiography (OPG) showed that both jaws were partially toothless with terminal stage of periodontitis of the remaining teeth. Also, OPG showed sharply limited semicircular defect in the retromolar region and along the front edge of the mandible rami. Conventional histopathologic examination of the neck masses showed malignant ameloblastoma which contained central fields of squamous differentiation. Immunoreactivity of several markers was determined using immunohistochemical analyses. After these diagnostic methods a definite histopathology diagnosis was made: Ameloblastoma metastaticum in textus fibroadiposus regio colli (typus acanthomatosus). CONCLUSION: It is not possible to distinguish conventional, ie intraosseous, ameloblastoma from malignant ameloblastoma according to histopathologic features. It is necessary to pay special attention, especially in elderly patients, and to carry out further clinical, radiological and pathohistological diagnostic procedures, such as immunohistochemical analysis. A timely and correct diagnosis and treatment of malignant ameloblastoma require a multidisciplinary approach.

[Correlation between disease progression and histopathologic criterions of the lip squamous cell carcinoma].

BACKGROUND/AIM: The most common malignancy of the lip is squamous cell carcinoma (SCC). In our population, according to epidemiological data, almost a half of all (45%) SCC of oral mucous tissue spreads over the lower and upper lip. The aim of this study was to estimate prognostic importance of histopathologic characteristics--histologic grade, nuclear grade and tumor size in relation to the appearance of lymph node metastases and relapse in SCC of the lip. METHODS: In the retrospective-prospective study 70 cases of lower and upper lip SCC were analyzed. They were diagnosed from 2002 to 2006 in the Clinic of Maxillofacial Surgery, Clinical Center of Montenegro. The data about localization of the carcinomas, histopathologic characteristics and lymph node status were taken from medical files of the patients. The patients were followed up in a 3-year period and the disease relapse or/and metastatic disease appearance were registereds. RESULTS: There was statistically significant difference in tumor size among the patients with and without disease relapse (p = 0.027). Logistic regression analysis showed that the tumor size is a statistically significant factor (R = 0.186; p = 0.011) for the appearance of regional lymph node metastases. Relative risk [exp (B)] for the appearance of regional lymph node metastases in relation to tumor size was 2.807. CONCLUSION: Histologic and nuclear grade of lip SCC are not prognostic factors for the appearance of the disease relapse and regional lymph node metastases. Tumor size is a predictive factor of the relapse appearance, as well as for lymph node metastases appearance. In clinical practice, tumor size is a factor that classifies patients with lip SCC into the groups of higher and smaller risk of relapse appearance and for lymph node metastases appearance. Our results suggest that, risk for lymph node metastases appearance increases 2.8 times with increasing of the tumor size over 2 cm in diameter.