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.

Aetiology and use of antibiotics in pregnancy-related infections: results of the WHO Global Maternal Sepsis Study (GLOSS), 1-week inception cohort.

BACKGROUND: Pregnancy-related infections are important contributors to maternal sepsis and mortality. We aimed to describe clinical, microbiological characteristics and use of antibiotics by source of infection and country income, among hospitalized women with suspected or confirmed pregnancy-related infections. METHODS: We used data from WHO Global Maternal Sepsis Study (GLOSS) on maternal infections in hospitalized women, in 52 low-middle- and high-income countries conducted between November 28th and December 4th, 2017, to describe the frequencies and medians of maternal demographic, obstetric, and clinical characteristics and outcomes, methods of infection diagnosis and causative pathogens, of single source pregnancy-related infection, other than breast, and initial use of therapeutic antibiotics. We included 1456 women. RESULTS: We found infections of the genital (n = 745/1456, 51.2%) and the urinary tracts (UTI) (n = 531/1456, 36.5%) to be the most frequent. UTI (n = 339/531, 63.8%) and post-caesarean skin and soft tissue infections (SSTI) (n = 99/180, 55.0%) were the sources with more culture samples taken and microbiological confirmations. Escherichia coli was the major uropathogen (n = 103/118, 87.3%) and Staphylococcus aureus (n = 21/44, 47.7%) was the commonest pathogen in SSTI. For 13.1% (n = 191) of women, antibiotics were not prescribed on the same day of infection suspicion. Cephalosporins (n = 283/531, 53.3%) were the commonest antibiotic class prescribed for UTI, while metronidazole (n = 303/925, 32.8%) was the most prescribed for all other sources. Ceftriaxone with metronidazole was the commonest combination for the genital tract (n = 98/745, 13.2%) and SSTI (n = 22/180, 12.2%). Metronidazole (n = 137/235, 58.3%) was the most prescribed antibiotic in low-income countries while cephalosporins and co-amoxiclav (n = 129/186, 69.4%) were more commonly prescribed in high-income countries. CONCLUSIONS: Differences in antibiotics used across countries could be due to availability, local guidelines, prescribing culture, cost, and access to microbiology laboratory, despite having found similar sources and pathogens as previous studies. Better dissemination of recommendations in line with antimicrobial stewardship programmes might improve antibiotic prescription.

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.

Oxidative-Stress Related Gene Polymorphism in Endometriosis-Associated Infertility.

Background and Objectives: Endometriosis is a benign inflammatory disease associated with infertility and chronic pelvic pain, estimated to affect 7−10% of reproductive-age women, with the possibility of malignant transformation. Recent studies focus on oxidative stress and genetic mutations as risk factors in the pathophysiology of endometriosis-associated infertility. Materials and Methods: This case-control study is the first in Eastern European women that aimed to investigate four genes' genetic polymorphisms that encode antioxidant enzymes involved in oxidative stress (glutathione peroxidase 1, GPX1 198Pro > Leu, catalase CAT-262C > T, glutathione S-transferase M1, and T1 null genotype) and their association with endometriosis-related infertility. We compared 103 patients with endometriosis-associated infertility with 102 post-partum women as the control group. Results: The endometriosis group had a mean age of 34.5 +/− 6.12 years, while the control group's mean age was 35.03 +/− 5.95 years. For CAT-262C > T polymorphism, the variant genotypes were significantly more frequent in the endometriosis group. Moreover, for the GPX1 198Pro > Leu, the endometriosis group had significantly more frequent CT and TT genotypes. The null genotype of GSTM1 was detected significantly higher in the endometriosis group. No significant differences were found in the frequency of GSTT1 between the two groups. This study suggests that GPX1 198Pro > Leu, CAT-262C > T, and GSTM1 polymorphisms may be risk factors and that the association between the GSTM1-GSTT1 null genotype may play a significant role in endometriosis-associated infertility. Moreover, this study suggests that the GSTT1 null genotype does not influence the disease. Visual identification of endometriotic lesions with microscopic confirmation is the accepted gold standard for diagnosing endometriosis, but general anesthesia and laparoscopy are required. Conclusions: In this regard, a panel of genetic or laboratory markers is needed for the early diagnostics of this prevalent disease, especially in the case of young patients with future pregnancy intention.

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.

Perinatal outcomes among births to women with infection during pregnancy.

OBJECTIVE: This study is part of the Global Maternal Sepsis Study (GLOSS). It aimed to estimate neonatal near-miss (NNM) and perinatal death frequency and maternal risk factors among births to women with infection during pregnancy in low-income and middle-income countries (LMIC). DESIGN: We conducted a 1-week inception hospital-based cohort study. SETTING: The study was carried out in 408 hospitals in 43 LMIC of all the WHO regions in 2017. PATIENTS: We included women with suspected or confirmed infection during pregnancy with at least 28 weeks of gestational age up to day-7 after birth. All babies born to those women were followed from birth until the seventh day after childbirth. Perinatal outcomes were considered at the end of the follow-up. MAIN OUTCOME MEASURES: Perinatal outcomes were (i) babies alive without severe complication, (ii) NNM and (iii) perinatal death (stillbirth and early neonatal death). RESULTS: 1219 births were analysed. Among them, 25.9% (n=316) and 10.1% (n=123) were NNM and perinatal deaths, respectively. After adjustment, maternal pre-existing medical condition (adjusted odds ratios (aOR)=1.5; 95% CI 1.1 to 2.0) and maternal infection suspected or diagnosed during labour (aOR=1.9; 95% CI 1.2 to 3.2) were the independent risk factors of NNM. Maternal pre-existing medical condition (aOR=1.7; 95% CI 1.0 to 2.8), infection-related severe maternal outcome (aOR=3.8; 95% CI 2.0 to 7.1), mother's infection suspected or diagnosed within 24 hours after childbirth (aOR=2.2; 95% CI 1.0 to 4.7) and vaginal birth (aOR=1.8; 95% CI 1.1 to 2.9) were independently associated with increased odds of perinatal death. CONCLUSIONS: Overall, one-third of births were adverse perinatal outcomes. Pre-existing maternal medical conditions and severe infection-related maternal outcomes were the main risk factors of adverse perinatal outcomes.

Laparoscopic Resection of Diaphragmatic Endometriosis in 10 Steps.

STUDY OBJECTIVE: Laparoscopic resection of diaphragmatic endometriosis has the advantages of a minimally invasive approach [1]. The standardization and description of the technique are the main objectives of this video. We described the procedure in 10 steps to make it easier and safer. DESIGN: A step-by-step video demonstration of the technique (Video 1). SETTING: A French university tertiary care hospital. PATIENTS: Patients with diaphragmatic endometriosis confirmed by magnetic resonance imaging [2]. The local institutional review board ruled that approval was not required for this video article because the video describes a technique and does not report a clinical case. INTERVENTION: There are no guidelines on the surgical treatment of diaphragmatic endometriosis [3]. We propose a laparoscopic approach using a right lateral access with the patient in the left lateral decubitus position [4]. MEASUREMENTS AND MAIN RESULTS: This video presents the procedure divided into the following 10 steps: step 1, set up; step 2, patient position; step 3, installation of the trocars; step 4, releasing the liver; step 5, exposure of the diaphragmatic endometriosis; step 6, making a diaphragmatic defect; step 7, exploring the thoracic cavity; step 8, resection of diaphragmatic endometriosis; step 9, inserting the suction catheter; and step 10, closing the diaphragmatic defect. CONCLUSION: Standardization of laparoscopic resection of diaphragmatic endometriosis could make this procedure easier and safer to perform. The left lateral decubitus position helps to have complete exposure of the right diaphragmatic muscle and endometriosis. We presented 10 steps to help perform each part of the surgery in logical sequence, making the procedure ergonomic and easier to adopt and learn [5]. Standardization of laparoscopic techniques could help to reduce the learning curve.