Cervical intraepithelial neoplasia grade 2 (CIN2) is an intermediate stage between CIN 1, which is a low-grade lesion, and CIN3, which is the immediate precursor of cervical cancer (CC). ...Traditionally, CIN2 was regarded as a high-grade lesion and was treated with conization or ablative methods. In recent years, there has been a shift in the management of younger patients, who are now more often being managed conservatively due to frequent spontaneous CIN2 regression and possible adverse effects of treatment on future pregnancies. Because the risk of progression to CC still exists with conservative management, a personalized approach is needed to identify patients with a higher probability of progression. In this regard, research has focused on the role of host and human papillomavirus (HPV) gene methylation. This systematic review summarizes the current knowledge regarding conservative CIN2 management focusing on the main methylation markers and its implementation in conservative CIN2 management, and it describes major ongoing longitudinal studies on the subject. The review showed that DNA methylation is an accurate predictor of disease progression and a valid triage tool for HPV-positive women, with CIN2 performing better than triage cytology. Because virtually all CCs are methylation-positive, methylation-negative women at baseline have an extremely low risk of CC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background: This two-armed clinical audit aimed to evaluate the effectiveness of vaginal tamponade in reducing postoperative bleeding after large loop excision of the uterine cervix’s transformation ...zone (LLETZ). Methods: We included patients after LLETZ with and without vaginal tamponade in this clinical audit analysis. In January 2021, we stopped performing routine postoperative vaginal tamponade after LLETZ, intensively monitored the occurrence of bleeding 30 days after the procedure, and analyzed the clinical audit. We compared the data with the clinical audit from 2016, when we performed routine postoperative tamponade in all patients. The primary outcome of our analysis was to evaluate the effect of vaginal tamponade on reducing the incidence of postoperative bleeding, necessitating secondary intervention. The secondary outcome was the occurrence of postoperative infection necessitating antibiotic treatment. All patients in the study signed written consent to analyze their data for quality control. Results: A total of 301 patients (132 patients with and 169 patients without postoperative tamponade) were included in the study and were similar regarding baseline characteristics. Postoperative bleeding occurred in 16 (5.3%) patients of both groups and was more prevalent in patients with vaginal tamponade compared to patients without the tamponade, although the difference was not statistically significant (6.1% vs 4.7%, respectively, p = 0.616). Postoperative infection occurred in 8 (2.7%) patients of both groups, and the incidence was similar in both groups (3.0% vs 2.4%, respectively, p = 0.734). Conclusions: According to our results, routine tamponade after LLETZ does not help reduce the incidence of postoperative bleeding.
(1) Background: There are limited data on the success of conservative treatment of high-grade cervical squamous intraepithelial lesions (HSIL) with imiquimod directly compared to standard of ...treatment with LLETZ. (2) Methods: Patients aged 18-40 with histological HSIL (with high-grade cervical intraepithelial neoplasia, CIN2p16+ and CIN3), were randomly assigned to treatment with imiquimod or LLETZ. The primary outcome was defined as the absence of HSIL after either treatment modality. The secondary outcomes were the occurrence of side effects. (3) Results: 52 patients were allocated in each group and were similar regarding baseline characteristics. In the imiquimod group, 82.7% of patients completed treatment, which was successful in 51.9%. All patients in the LLETZ group completed treatment, which was successful in 92.3% (
< 0.001). In the subgroup of CIN2p16+ patients, treatment with imiquimod was not inferior to LLETZ (73.9% vs. 84.2%,
= 0.477). During and after treatment, no cases of progression to cancer were observed. Side effects and severe side effects (local and systemic) were more prevalent in the imiquimod than in the LLETZ group (88.5% vs. 44.2% (
-value < 0.001) and 51.9% vs. 13.5% (
-value < 0.001), respectively). (4) Conclusion: Generally, in patients with HSIL, LLETZ remains the gold standard of treatment. However, in a subgroup analysis of patients with CIN2p16+, the success rate was comparable between the two treatment modalities. Due to the prevalence of side effects, the treatment compliance with imiquimod use may, however, present a clinically important issue.
The association between vitamin D deficiency and various adverse pregnancy outcomes has been extensively investigated in recent years. The pregnant woman is the only source of vitamin D for the ...foetus. The main sources of vitamin D for pregnant women are sunlight, fortified dairy products, oily fish and dietary supplements. Vitamin D deficiency during pregnancy has been associated with some adverse neonatal outcomes as well as an increased risk of late pregnancy complications. The outcomes of the published studies investigating preeclampsia and gestational diabetes mellitus vary with some large trials suggesting a potential positive effect of vitamin D supplementation during pregnancy on the decreased risk of these complications. Research also suggests a possible connection between lower vitamin D concentrations and increased risk of preterm labour. In our manuscript, we aim to review the existing literature regarding the prevalence of vitamin D deficiency during pregnancy, the factors associated with vitamin D deficiency, and possible pregnancy complications arising from it.
Cervical cancer screening has enabled a decrease in the incidence and mortality of cervical cancer. Various screening modalities have been studied to date. In many countries, screening is still based ...on cervical cytology, where cervical cells obtained either on glass or in a liquid medium are examined under a microscope. However, the fact that the vast majority of cervical cancers are a result of persistent infection with high-risk human papillomaviruses (hr-HPV) has led to the implementation of primary HPV screening in many countries. Taking into consideration the fact that the majority of HPV infections are transient and do not cause cervical precancer, effective triage methods are needed to prevent an increase in colposcopy referrals. Among these, the most extensively investigated are HPV genotyping, HPV methylation, and p16/Ki67 dual staining. In this manuscript, we briefly summarize the current knowledge regarding different screening strategies for the prevention of cervical cancer, with a focus on p16/Ki67 dual staining. In addition, we provide an explanation regarding the rationale for the use of various screening modalities based on the molecular biology of cervical cancer and cervical precancerous lesions.
Cervical intraepithelial neoplasia grade 2 (CIN2) is an intermediate stage between CIN 1, which is a low-grade lesion, and CIN3, which is the immediate precursor of cervical cancer (CC). ...Traditionally, CIN2 was regarded as a high-grade lesion and was treated with conization or ablative methods. In recent years, there has been a shift in the management of younger patients, who are now more often being managed conservatively due to frequent spontaneous CIN2 regression and possible adverse effects of treatment on future pregnancies. Because the risk of progression to CC still exists with conservative management, a personalized approach is needed to identify patients with a higher probability of progression. In this regard, research has focused on the role of host and human papillomavirus (HPV) gene methylation. This systematic review summarizes the current knowledge regarding conservative CIN2 management focusing on the main methylation markers and its implementation in conservative CIN2 management, and it describes major ongoing longitudinal studies on the subject. The review showed that DNA methylation is an accurate predictor of disease progression and a valid triage tool for HPV-positive women, with CIN2 performing better than triage cytology. Because virtually all CCs are methylation-positive, methylation-negative women at baseline have an extremely low risk of CC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Vitamin D is a lipid soluble vitamin involved primarily in calcium metabolism. Epidemiologic evidence indicates that lower circulating vitamin D levels are associated with a higher risk of ovarian ...cancer and that vitamin D supplementation is associated with decreased cancer mortality. A vast amount of research exists on the possible molecular mechanisms through which vitamin D affects cancer cell proliferation, cancer progression, angiogenesis, and inflammation. We conducted a systematic review of the literature on the effects of vitamin D on ovarian cancer cell.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Very limited information exists about the role of p16/Ki67 dual staining on glandular cells in detecting glandular precancerous lesions and cervical adenocarcinoma. In this study, we investigated the ...diagnostic accuracy of p16/Ki67 dual staining for the detection of glandular and squamous lesions on the uterine cervix and for cancer of the upper reproductive tract. We performed a retrospective analysis of prospectively collected data on 96 patients with glandular cell abnormalities. We analyzed the diagnostic accuracy of p16/Ki67 dual staining for atypical glandular cells, not otherwise specified (AGC-NOS); atypical glandular cells, favor neoplastic (AGC-FN); adenocarcinoma in situ (AIS); and A-CA (cervical adenocarcinoma). A separate analysis for the detection of squamous precancerous lesions and squamous-cell carcinoma (CIN3+) and for cancer of the upper reproductive tract (EC/OC) was performed. Among patients who had normal histology or a low-grade lesion on final analysis, only 8.5% had positive dual staining. On the other hand, 85.7% of patients with AIS+ on final histology had positive dual staining. The respective specificities of p16/Ki67 dual staining on AGC-NOS for the detection of AIS+ (adenocarcinoma in situ or cervical adenocarcinoma), CIN3+ and EC/OC were 91.5%, 88.7% and 86.4%. High specificity values of p16/Ki67 dual staining on cervical smears labelled as AGC-NOS for the detection of CIN3+ and AIS+ suggest that this method might be a useful addition in cervical cancer screening.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The interpretation of postmenopausal smears and the gynecological treatment of these patients can often be difficult. The objective of this study was to assess the performance of p16/Ki-67 ...dual-stained cytology as a triage of atypical squamous cells of undetermined significance and low-grade intraepithelial lesion cytology results in postmenopausal women.
All consecutive atypical squamous cells of undetermined significance and low-grade intraepithelial lesion smears in 1-year period were collected and p16/Ki-67 immunostaining was performed retrospectively. The results were compared with histology results or long-term cytology follow-up in cases with no biopsy.
The sensitivity of p16/Ki-67 immunostaining for the detection of cervical intraepithelial neoplasia (CIN) 2 and CIN 3 was 57.1% and 85.0%, respectively. The specificity for the detection of CIN 2 was 94.3% and CIN 3 92.4%. Negative predictive values for the detection of CIN 2 and CIN 3 were 96.3% and 99.6%, respectively.
Dual p16/Ki-67 immunostaining is a useful additional method in postmenopausal patients with low-grade cytology. Considering the high specificity and negative predictive value in our study, we believe that it could be helpful in avoiding unnecessary referrals to colposcopy and thus reduce the cost of the program.
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