The importance of combined HPV and CINtec® PLUS genotyping testing for p16 in women with cervical squamous cell carcinoma.

INTRODUCTION: Immunohistochemistry (IHC) for p16INK4A (p16) is a reliable surrogate test for the presence of a high-risk, potentially transformative human papillomavirus (HPV) infection in precursor and malignant lesions of the cervix. The purpose of this study was to evaluate changes in cervical cells caused by persistent HPV infection, by IHC (p16 protein) by comparison with HPV genotyping. PATIENTS, MATERIALS AND METHODS: The study included female patients aged between 26 and 57 years who presented to a public hospital, with complaints related to the genital area, namely vaginal bleeding and dyspareunia. After selecting the patients, samples were subjected to cytological testing and IHC for p16 and for the determination of HPV types. RESULTS: The relationship between HPV status and p16 status was statistically significant (p=0.0001), of the 41 patients, 53.7% were HPV positive, respectively 56.1% were p16 positive, the agreement relationship between the two indicators was very high (weighted kappa: 0.951). The clinical performance of CINtec® PLUS triage for p16 shows a high positive predictive value (PPV) and a high negative predictive value (NPV) of 95.7% and 100%, respectively, as regards HPV. CONCLUSIONS: The p16 marker (CINtec® PLUS) can be used as a prognostic biomarker and provides clinical usefulness through increased sensitivity (Se) and specificity (Sp) in the triage of women at risk of developing precancerous lesions, compared to cytology that is based on morphology, but has a rather low Se and high Sp, while HPV testing is very sensitive but slightly more specific.

The Hybrid Capture 2 Results in Correlation with the Pap Test, Sexual Behavior, and Characteristics of Romanian Women.

BACKGROUND: Human papillomavirus (HPV) infection is the major cause of cervical cancer (CC); hence, it is critical to understand the processes by which HPV infection causes squamous intraepithelial lesions, as well as the proper diagnostic tools. The objective of this study was to establish the correlations between Pap test results and Hybrid Capture 2 (HC2) tests findings. MATERIALS AND METHODS: This study included 169 women between the ages of 30 and 64, who presented for consultation in gynecological clinics in both the public and the private sectors. These women reported symptoms, such as abnormal vaginal discharge and genital irritation, as well as early onset of sexual activity, multiple sexual partners, history of other sexually transmitted infections or high-risk sexual partners, immunosuppression, or tobacco smoking. Pap tests and HPV testing, using the HC2 method, were performed for the women enrolled in the study, including data gathered after patients completed questionnaires concerning their sexual behavior. RESULTS: The HC2 method revealed that 66 patients (39.1%) tested positive for high-risk HPV types. Of the patients with positive results, 14 (21.2%) presented Atypical Squamous Cells of Undetermined Significance (ASC-US) compared to 10 (9.7%) patients in the negative group (p = 0.042). Atypical Squamous Cells for which a high-grade lesion cannot be excluded (ASC-H) were identified primarily in women with positive HC2 (6.1%). HR-HPV positivity was substantially more associated with low-grade ASC-US or low-grade squamous intraepithelial lesion (LSIL) and high-grade ASC-H cytology (OR = 2.53; 95% CI: 1.10-5.80, respectively, OR = 14.9; 95%CI: 1.006-34.59). Unmarried women (31.8%; p = 0.004) and women with multiple partners (over four partners, 10.6%; p = 0.03) were more likely to have an HPV infection when compared to married women and those with fewer sexual partners. CONCLUSIONS: Understanding the epidemiology of HPV genital infections is essential for developing preventive measures against this infection and CC. Identifying the most prevalent HPV types, and determining the incidence of HPV oncogenic infections, in conjunction with Pap test results and sexual behavior information, can constitute part of an algorithm for the efficient management of cervical intraepithelial lesions.

Assessing the Level of Knowledge, Beliefs and Acceptance of HPV Vaccine: A Cross-Sectional Study in Romania.

(1) Background: The infection with Human papilloma virus (HPV) is the most common sexually transmitted infection and it has been associated with cervical cancer (CC) in 99.7% of the cases. In Romania, CC is the second most common, with incidence (22.6%000) and mortality rates (9.6%000) three times higher than any other European country. Our aim was to assess the level of knowledge regarding HPV infection among parents, highschool students, medical students and doctors, with an emphasis on their main source of information-the Internet. (2) Methods: We applied five questionnaires to six categories of respondents: parents of pupils in the 6th-8th grades, medical students, doctors, boys in the 11th-12th grades, girls in the 11th-12th grades and their mothers. (3) Results: We included a total of 3108 respondents. 83.83% of all respondents had known about HPV infection. The level of information about HPV infection and vaccination was either satisfactory, poor or very poor. Their main source of information varied depending on the respondent profile and professional activity. Medical students were informed by doctors and healthcare professionals (53.0%), doctors gathered their information from books, journals and specialized brochures (61.6%). For the other categories of respondents, the Internet was the main source of information. Most respondents answered that doctors and healthcare professionals should provide information on HPV infection and vaccination, but very few of them actually seeked information from their general practitioner. (4) Conclusions: Population adherence to the appropriate preventative programs, as well as relevant information disseminated by the medical staff are key elements towards reducing the risk of HPV-associated cancers. An important role could also be played by schools, where teachers and school doctors could provide relevant information on the general aspects of HPV infection. Additionally, sex education classes and parent-teacher meetings should cover the main characteristics of HPV infection and what preventative measures can be employed against it.

Risk stratification of papillary thyroid microcarcinomas via an easy-to-use system based on tumor size and location: clinical and pathological correlations.

INTRODUCTION: We aimed to determine whether two clinically accessible parameters, tumor size and location within the thyroid, correlate with clinicopathological features that are predictors of high risk in papillary thyroid microcarcinomas (PTMCs). MATERIALS AND METHODS: PTMC cases were obtained from the database of the Department of Pathology, Emergency County Hospital, Târgu Mures, Romania. Four tumor groups were created based on tumor size and location: Group I (≥5 mm, subcapsular), Group II (≥5 mm, nonsubcapsular), Group III (<5 mm, subcapsular), and Group IV (<5 mm, nonsubcapsular) PTMCs. Clinicopathological features and follow-up data were compared by univariate and multivariate analysis. RESULTS: Our study included 164 PTMCs (n=70/20/19/55 in Groups I∕II∕III∕IV, respectively). High-grade morphological features, such as plump pink cells (p=0.010), tumor desmoplasia (p=0.022) and sclerosis (p=0.001), infiltrative tumor borders (p=0.005), positive resection margins (p=0.005), invasion into the perithyroid adipose tissue (p=0.001), irregular nuclear membranes (p=0.004), and pseudoinclusions (p=0.001) were significantly more prevalent among Group I PTMCs. Group IV PTMCs were characterized by a paucity of the above-mentioned morphological features, while Group II and III PTMCs displayed intermediate morphological profiles. CONCLUSIONS: Group I PTMCs proved to be associated with more aggressive morphological features and might need a more careful clinical approach.

Histopathological predictive factors for the overall survival rate in patients with urothelial carcinoma of the bladder treated by radical cystectomy: a Romanian cohort study.

INTRODUCTION: Urothelial carcinoma (UC) variants are considered as having a more aggressive behavior and a more advanced stage at presentation than conventional UC. However, the evidence supporting the role of UC variants on overall survival (OS) is conflicting. We aimed to assess the impact of demographic factors (age at surgery, gender) and tumor characteristics [conventional∕variant UC, associated carcinoma in situ (CIS), associated papillary component, Tumor, Node, Metastasis (TNM) staging, positive surgical margins] on OS in a series of patients treated for UC in our Department. PATIENTS, MATERIALS AND METHODS: We performed a retrospective, cohort study and included 69 UC patients treated by radical cystectomy (RC) in our Department over an eight-year period, with complete follow-up information. Associations of UC variants as well as demographic and morphological factors with OS were assessed using univariable and multivariable Cox analysis. RESULTS: Our data showed that UC variants were statistically significantly associated with the presence of distant metastases (p=0.036) and positive surgical margins (p=0.009), but had no influence on OS (p=0.504). Further on, we demonstrated that age at surgery (p=0.045), tumor stage (p=0.012), lymph node involvement (p=0.009), and presence of positive surgical margins (p=0.002) had a statistically significant influence on OS both by univariable and multivariable Cox analysis. CONCLUSIONS: Age, tumor stage and lymph node involvement, as well as positive surgical margins represent prognostic factors in RC patients. UC variants were more likely to be associated to metastases and positive surgical margins but had no influence on OS.

Malignant melanoma - the most severe skin cancer and neurological pathology.

OBJECTIVE: We report our clinical experience with malignant melanoma (MM) patients associated with neurological involvement. PATIENTS, MATERIALS AND METHODS: A database of patients admitted from 2014-2019 in the Ist Clinic of Neurology, Emergency County Hospital of Târgu Mures, Romania, was reviewed to identify patients with MM and neurological involvement. We assessed the demographic and clinical data regarding the neurological disorders and the primary tumor characteristics from the patient registries. Both histopathological and immunohistochemical analysis of the neoplasm was available for the entire cohort. RESULTS: We analyzed 13 982 patient files and 21 met all the inclusion and exclusion criteria. Brain metastases were found in 38.09% of the patients, spinal metastases in 9.52% of the patients, ischemic stroke by cancer-associated thrombosis in 42.85% of the patients and peripheral nervous system involvement in 19.04% of the patients. No statistically significant differences between the four categories of neurological disorders according to socio-demographic parameters, location of the primary tumor, existence of primary tumor ulceration, invasion of the lymph nodes or the presence and location of distant metastasis was found (p>0.05). Our presented patient is the first case of uveal melanoma with hemorrhagic brain metastasis before hepatic involvement. CONCLUSIONS: Neurological involvement in MM encompasses a myriad of variants and while the clinical setting varies from one patient to another, an underlining neoplasia should be evaluated in suspected patients.

The role of clinical and pathological assessment in choosing the best therapeutic management to improve survival in rectal cancer.

The main target in rectal cancer management is an individualized therapeutic strategy, based on tumor and patient characteristics. The assessment of clinical and pathological factors is important because they represent powerful predictors of the postoperative outcome and have to be considered in the decision making regarding the appropriate surgical technique. The aim of the study was to analyze how the tumor clinical and pathological features correlate with the chosen type of surgical intervention in influencing survival of rectal cancer patients. We ran a retrospective study on 289 patients (N=289) surgically treated for rectal cancer. We analyzed the individual influence of the studied parameter on survival rate in multivariate analysis and we also grouped them in associations of parameter variations and performed a survival analysis for prognostic univariate analysis. For patients with vascular and lymphatic invasion and without perineural invasion, choosing a sphincter function preserving technique brought a better long-term outcome. The TNM stages showed the strongest statistically significant effect upon survival. Patients in T3 or T4 stage benefited best from a performed sphincter saving technique and the positive effect was even higher for those in N1 stage. Assessment of pathological parameters, in association with the type of the surgical procedure, has a strong predictive value upon survival. Sphincter function preserving techniques are followed by good long-term outcome. Accurate preoperative staging can help in choosing the best individualized therapeutic management improving the life expectancy of patients with rectal cancer.

Ultrasonography-histopathology correlation in major salivary glands lesions.

Major salivary glands display a various and complex pathology, showing different evolution and prognosis, depending on the histopathological form. The choice of an appropriate treatment plan for the best outcome, therefore the proper surgical approach, would imply preoperative knowledge of the histopathological diagnosis. However, any core-biopsy performed prior to surgery presents the risk of a false result and increases the difficulty of latter surgery. Therefore, some complementary examinations are used, among these, ultrasonography. The retrospective study (April 2010-March 2013) conducted in the Clinic of Oral and Maxillofacial Surgery, Emergency County Hospital, Tirgu Mures, Romania, aims to evaluate the relevance of the ultrasonography by itself in leading towards a proper preoperative assessment and diagnosis, and thus, in choosing the proper treatment plan. The study included 33 lesions of the major salivary glands, undergoing first ultrasonography, then curative surgery. Different characteristics (shape, dimension, consistency, vascularization, homogeneity, delimitation) were assessed on ultrasonography as well as on histopathology; finally, the correlation between those two examinations was evaluated, by comparing diagnoses. The results of our study are similar to others, showing that ultrasonography can diagnose preoperatively the majority lesions of major salivary glands. The conclusions of the study sustain the importance of ultrasonography as a routine examination in major salivary glands lesions.