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.

Antibiotic Consumption in Hospitals and Resistance Rate of Klebsiella pneumoniae and Escherichia coli in Montenegro.

Inappropriate use of antibiotics leads to an increase in antibiotic resistance. Infections caused by antibiotic-resistant gram-negative bacteria are a serious threat to public health. This study aimed to compare data on inpatient antibiotic consumption with antimicrobial resistance (AMR) rate of Klebsiella pneumoniae and Escherichia coli invasive strains in Montenegro and provide targets for improving antibiotic use. We used the national data on antibiotic consumption from 2009 to 2015, Point Prevalence Survey data on inpatient antibiotic consumption from 2015, and national AMR data on 79 Klebsiella pneumoniae and 68 Escherichia coli isolates collected from 8 hospitals from 2016 to 2018. The most commonly used antibiotics were third-generation cephalosporins with a median annual consumption of 0.66 DDD/1000/day. Ceftriaxone was the most frequently prescribed antibiotic in the treatment of community/hospital acquired infections and surgical/medical prophylaxis. The highest resistance rates were recorded for Klebsiella pneumoniae to ceftriaxone, ceftazidime and gentamicin (93.59%, 90.79% and 89.87%, respectively), and Escherichia coli to aminopenicillins, ceftriaxone and ceftazidime (89.06%, 70.15% and 61.54%, respectively). High consumption of broad-spectrum antibiotics in Montenegro is accompanied by the high rate of resistance of Klebsiella pneumoniae and Escherichia coli to these agents. Antibiotic misuse demands the introduction of an antimicrobial stewardship program in Montenegrin hospitals.

Presence of histopathological premalignant lesions and infection caused by high-risk genotypes of human papillomavirus in patients with suspicious cytological and colposcopy results: A prospective study.

Background/Aim: In patients with premalignant cervical lesions, human papillomavirus (HPV) infection, at any moment, may be spontaneously eliminated, or may persist or transform cervical epithelium from a lower to a higher degree. Due to that, it is necessary to wisely select the patients who are at high risk of cancer development. The aim of the study was to establish the interdependence between a suspicious Papanicolaou (Pap) test and colposcopy with the infection caused by high-risk genotypes of human papillomavirus and the presence of premalignant cervical lesions. Methods: This prospective study used cytological, colposcopy, real-time polymerase chain reaction (PCR) of high-risk genotypes of human papillomavirus and histopathological analysis of cervical biopsy specimen. Out of 2,578 female patients sent to cytological analyses in Clinical Center of Montenegro, during 2012, 2013 and 2014, the study included 80 women who had to submit their biopsy specimens due to a suspicious Pap test and atypical colposcopy results. Results: In the group of 80 (3.1%; n = 80/2,578) of the selected female patients with suspicious Pap test and colposcopy, 2/3 or 56 (70%) of them had cervicitis, and 1/3 or 24 (30%) had cervical intraepithelial neoplasia. The most common type in cervical intraepithelial neoplasia was HPV16 in 8 female patients, ie 61.53% out of the number of infected, or 33.33% out of the total number of premalignant lesions Conclusion: Patients with suspicious Papanicolaou test, colposcopy results and infection which is caused by high-risk HPV infection (HPV 16 in particular) often have premalignant cervical lesions. In these cases, histopathological confirmation of lesions is mandatory, since it serves as a definitive diagnostic procedure.