The efficacy of topical imiquimod in high-grade cervical intraepithelial neoplasia: A systematic review and meta-analysis.

OBJECTIVE: A major side effect of cervical excision for high-grade cervical intraepithelial neoplasia (CIN) is premature birth. A non-invasive treatment for reproductive age women is warranted. The aim of the present study was to determine the efficacy of topical imiquimod in the treatment of high-grade CIN, defined as a regression to ≤CIN 1, and to determine the clearance rate of high-risk human papillomavirus (hr-HPV), compared with surgical treatment and placebo. METHODS: Databases were searched for articles from their inception to February 2023.The study protocol number was INPLASY2022110046. Original studies reporting the efficacy of topical imiquimod in CIN 2, CIN 3 or persistent hr-HPV infections were included. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist. RESULTS: Five studies were included (n = 463). Histological regression to ≤CIN 1 was 55% in imiquimod versus 29% in placebo, and 93% in surgical treatment. Imiquimod-treated women had a greater odds of histological regression to ≤CIN 1 than placebo (odds ratio [OR] 4.17, 95% confidence interval [CI] 2.03-8.54). In comparison to imiquimod, surgical treatment had an OR of 14.81(95% CI 6.59-33.27) for histological regression to ≤CIN 1. The hr-HPV clearance rate was 53.4% after imiquimod and 66% after surgical treatment (95% CI 0.62-23.77). CONCLUSIONS: The histological regression rate is highest for surgical treatment followed by imiquimod treatment and placebo.

Immunologic factors involved in the malignant transformation of endometriosis to endometriosis-associated ovarian carcinoma.

INTRODUCTION: Endometriosis is a risk factor for low-grade serous, clear cell, and endometroid ovarian carcinoma. In both endometriosis and ovarian carcinoma, immunological factors are associated with clinical outcome. Chronic inflammation in endometriosis may be linked to tumorigenesis, but exact processes contributing to endometriosis-associated ovarian carcinoma remain unknown. This review aims to describe potential immunological factors involved in the malignant transformation of endometriosis into ovarian carcinoma. METHODS: PubMed and Embase were searched from inception up to October 2020 for studies comparing immunological processes in endometriosis and endometriosis-associated ovarian carcinoma. RESULTS: Detailed analysis of immune components in the malignant transformation of endometriosis into endometriosis-associated ovarian carcinoma is lacking. Altered levels of chemokines and cytokines as IL-6, IL-8, IL-10, and TNF-α are reported and the function, number and polarization of NK cells, dendritic cells, and monocytes differ between endometriosis and associated ovarian carcinoma compared to healthy tissue. In addition, altered inflammasome and complement systems, indicate a role for the immune system in the carcinogenesis of endometriosis. CONCLUSION: Chronic inflammation in endometriosis may potentially drive inflammation-induced carcinogenesis in endometriosis-associated ovarian carcinoma. Exact immunological pathways and cellular processes remain unknown and require more thorough investigation.

Alterations in classical and nonclassical HLA expression in recurrent and progressive HPV-induced usual vulvar intraepithelial neoplasia and implications for immunotherapy.

Immunotherapy of usual vulvar intraepithelial neoplasia (uVIN) is promising; however, many patients still fail to show clinical responses, which could be explained by an immune escape through alterations in human leukocyte antigen (HLA) expression. Therefore, we analyzed a cohort of patients with a primary (n = 43) and subsequent recurrent uVIN lesion (n = 20), vaccine-treated uVIN patients (n = 12), patients with human papillomavirus (HPV)-induced vulvar carcinoma (n = 21) and healthy controls (n = 26) for the expression of classical HLA-class I/II and nonclassical HLA-E/-G and MHC class I chain-related molecule A (MICA). HLA-class I was downregulated in 70% of uVIN patients, including patients with a clinical response to immunotherapy. Downregulation of HLA-class I is probably reversible, as only 15% of the uVIN cases displayed loss of heterozygosity (LOH) and HLA-class I could be upregulated in uVIN keratinocyte cultures by interferon γ. HLA-class I downregulation is more frequently associated with LOH in vulvar carcinomas (25-55.5%). HLA-class II was found to be focally expressed in 65% of uVIN patients. Of the nonclassical molecules, MICA was downregulated in 80% of uVIN whereas HLA-E and -G were expressed in a minority of cases. Their expression was more prominent in vulvar carcinoma. No differences were found between the alterations observed in paired primary and recurrent uVIN. Importantly, downregulation of HLA-B/C in primary uVIN lesions was associated with the development of recurrences and progression to cancer. We conclude that downregulation of HLA is frequently observed in premalignant HPV-induced lesions, including clinical responders to immunotherapy, and is associated with worse clinical outcome. However, in the majority of cases downregulation may still be reversible.

The diagnostic and therapeutic approach of a primary bilateral leiomyoma of the ovaries: a case report and a literature review.

INTRODUCTION: A primary fibroid (leiomyoma) arising from both ovaries is rare and can be difficult to diagnose as a result of the low incidence and its indistinctive presentation. A literature review on the diagnostic and therapeutic approach of this rare benign tumour is presented. We describe a case of bilateral primary ovarian fibroid with an unusual presentation to illustrate our recommendations for treatment. CASE PRESENTATION: A 37-year-old woman was admitted with symptoms of acute severe abdominal pain. She had a history of faint abdominal discomfort. Due to the acute deterioration of the abdominal pain a diagnostic laparoscopy was performed. A tumour arising from both ovaries was seen and a biopsy was taken in order to decide on further therapy. Histology showed a fibroid for which excision by a second laparoscopic intervention was planned. Due to excessive adhesions conversion to laparotomy was necessary. CONCLUSION: We recommend that in the case of an abnormal adnexal mass, particularly in women who want to preserve their fertility, frozen section histology be performed laparoscopically. A frozen section diagnostic procedure, instead of a regular biopsy, seems to be a useful tool during an elective diagnostic laparoscopic procedure in order to prevent potential morbidity as a result of possible future laparoscopy or even laparotomy. Previous laparoscopic procedures can cause massive adhesions that could impede a subsequent laparoscopic approach.

The value of hysteroscopy in the diagnostic approach to a rudimentary horn pregnancy.

A 33-year-old woman presented with an ectopic pregnancy without any complaints. Laparoscopy was performed since a tubal pregnancy was expected. However, both fallopian tubes appeared normal and it was not possible to differentiate accurately between a pregnancy in a non-communicating horn and a pregnancy in a bicornuate uterus. We therefore performed MRI which showed a thin myometrium around the pregnancy. In order to differentiate between a communicating and a non-communicating uterine horn the authors performed a hysteroscopy. Since there was only one cervical os, and an entrance to the second uterine cavity was not seen along the cervical canal, it was concluded that this pregnancy was situated in a non-communicating rudimentary horn. The non-communicating uterine horn, with the pregnancy in situ, was completely removed. Since a pregnancy in a bicornuate uterus is viable in contrast to a pregnancy in a non-communicating horn, accurate diagnosis is important.