Mattia Dominoni

Palliative treatment of endometrial cancer: what is the role of anastrozole in elderly women?

Abstract Background Type I endometrial cancer is the most common gynaecological tumour in developed countries and its incidence is increasing also because of population aging. The aim of this work is to test the feasibility and safety of anastrozole as palliative treatment of endometrial cancer in elderly women ineligible for standard surgical treatment. Methods Patients with histological diagnosis of type I endometrial cancer not suitable for surgical treatment were enrolled in this pilot study. Anastrozole was administered 1 mg daily orally after performing an accurate clinical and radiological staging. Validated questionnaire and self-reported outcomes were used to evaluate quality of life and compliance during the study period. Results Eight patients with a mean age of 85 (range 80–88 years) were enrolled. All patients had endometrial cancer confined to the uterus, and none progression of disease was observed during the study period. A partial response to the therapy was reported in seven patients, while one patient had stable disease. Tumour symptoms improvement such as pain, vaginal bleeding and vaginal discomfort was reported. The endometrial thickness after twelve months has showed a reduction of 9.25 ± 4.77 mm. The average follow-up time was 18.25 months. Four women died for non oncological reasons, none death related to endometrial cancer was reported. Evaluation of symptoms showed a significant reduction of appetite loss and insomnia, while a significant increase of global health status and fatigue was reported. Conclusions Our preliminary data suggested that the palliative use of anastrozole may be a suitable therapy for the proper management of early stages endometrial cancer in elderly women not suitable for surgical treatment with good compliance and tolerance. Trial registration 2013000840. Date of registration: 21/09/2013. URL: trials.sanmatteo.loc .

Conservative Treatment of Uterine Myomas: A Network Meta-Analysis of Randomized Controlled Studies

To comparatively evaluate the effectiveness of uterine artery embolization (UAE), high-intensity focused ultrasound (HIFU), radiofrequency ablation treatment (RFT), and laparoscopic/laparotomic surgery in the conservative treatment of uterine fibroids. The research was performed via electronic databases PubMed, Embase, and Cochrane Library, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. The network included 10 randomized trials between 2000 and 2024 and 1002 randomized subjects. The network meta-analysis was conducted with subroutine netmeta on R. The risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials. The surface under the cumulative ranking curve (SUCRA) was computed by Bayesian network meta-analysis. Incidences of reintervention per 100 person/year of follow-up were 4.13 (range, 0-19.4), 16.1 (6.2-32.8), 14.3 (0-15.1), and 6 (4.3-6.7) for myomectomy, UAE, HIFU, and RFT, respectively. The incidence rate ratios compared with myomectomy were 2.45 (95% confidence interval [CI], 1.38-4.37), 5.23 (95% CI, 1.59-17.3), and 4.59 (95% CI, 0.77-27.3; p = .09) for UAE, HIFU, and RFT, respectively. RTF had the highest (SUCRA, 1.25% and 3%) whereas myomectomy had the lowest risk of reintervention (SUCRA, 98% and 95%) or hysterectomy during follow-up (median, 12 months; range, 3-24). The risk of major complications was significantly lower after UAE (odds ratio, 0.38; 95% CI, 0.17-0.85) than myomectomy. The procedure with the lowest likelihood of major complications was HIFU (SUCRA, 81.5%). Finally, in the evaluation of QoL at follow-up visits, there were no differences between the treatments studied, although the model was highly heterogeneous and inconsistent. In the analysis of randomized trials, surgical myomectomy carried the least risk of reintervention and subsequent hysterectomy during a relatively short follow-up period. HIFU was the method with the lowest risk of major complications.

The role of multiple high‐risk human papillomavirus infection on the persistence recurrence of high‐grade cervical lesions after standard treatment: A systematic review and a meta‐analysis

AbstractIntroductionThe role of multiple high‐risk human papillomavirus (HR‐HPV) infections on the occurrence of persistence/recurrence of high‐grade squamous intraepithelial lesion (HSIL) after conization/surgery for cervical intraepithelial neoplasia was evaluated.Material and methodsA systematic search of Pubmed/Medine, Scopus, Cochrane databases from inception to June 30, 2023 was performed. Three reviewers independently screened the abstracts of the selected studies and extracted data from full‐text articles. The data were subsequently tabulated and compared for consistency. The bias associated with each included study was evaluated according to the OSQE method. PROSPERO registration number CRD42023433022.ResultsOut of 1606 records screened, 22 full text articles met the inclusion criteria. A total of 8321 subjects treated (loop electrosurgical excision, laser or surgery) because of HSIL were followed‐up and included in the meta‐analysis. The pooled prevalence of overall persistence and/or recurrence was 17.6 (95% CI: 12.3–23.5) in multiple and 14.3 (95% CI: 10.1–19.2) in single HR‐HPV infections detected shortly before or at surgery. The pooled rate of multiple HR‐HPV infections was 25% (95% CI: 20.4–30). The odds ratio of histologically confirmed HSIL persistence and/or recurrence was significantly higher (OR: 1.38, 95% CI:1.08–1.75, p = 0.01, heterogeneity = 39%) among multiple than single HR‐HPV infections. Increased risk of HSIL persistence/recurrence was more marked among studies with multiple HR‐HPVs prevalence ≥25% (12 studies, N = 3476) (OR: 1.47, 95% CI: 1.18–1.84, heterogeneity = 0%) and in those evaluating true histologically confirmed recurrence after at least 6 months of negative follow‐up (9 studies, N = 5073) (OR: 1.67, 95% CI: 1.17–2.37, heterogeneity = 37%). Multiple HR‐HPVs infection detected during follow‐up visits had no effect on the risk of recurrence although the number of included studies was small (4 studies, N = 1248) (OR: 0.98, 95% CI: 0.68–1.39, heterogeneity = 0%). The risk of bias was rated as high in 10 and low‐moderate in 12 studies, respectively. In subgroup analysis, the risk of bias of the included studies (low/moderate vs. high), had a small, although not significant effect on the odds ratios of persistence/recurrence of HSIL (OR: 1.57, 95% CI: 1.23–2 for low‐moderate risk of bias and OR: 1.06, 95% CI: 0.65–1.75 for high risk of bias; p‐value for subgroup differences = 0.17).ConclusionsMultiple HR‐HPVs infections at the time of standard treatment of HSIL entail a small but significant increased risk of persistence/recurrence of HSIL and should be taken into account in the follow‐up plan.

Retrospective Study of the Risk of Progression to Squamous Cell Carcinoma of Vulvar Lichen Planus Forms Isolated or Associated With Other Dermatoses

ABSTRACT Aims The aim of the study was to examine the potential risk of vulvar lichen planus (LP), alone or associated with lichen sclerosus (LS) or lichen simplex chronicus (LSC), to evolve towards vulvar cancer (VSCC). Methods We retrospectively investigated the incidence of vulvar cancer in women diagnosed with LP, alone or associated with LS and LSC, between 2007 and 2022. Results We retrieved the data of 77 women with LP with a mean age of 63.5 ± 11.9 years old. Of these, 53 had LP, 19 had LP+LS, and 5 had LP+LSC. Ultrapotent topical corticosteroids were the first‐line treatment. The mean follow‐up time was 45 ± 30.14 months, during which four patients developed VSCC (5.19%). All four cases were found to be associated with the presence of multiple lichen, and the frequency of developing a neoplasm in the presence of LS or LSC superimposed on LP was found to be significant with Fisher's exact test ( p  = 0.0079). Conclusion Analyzing our data, we can point out a concrete possibility regarding the relationship between multiple lichen and VSCC compared to LP alone. However, the sample size is too small to allow definitive conclusions to be drawn, and multicenter studies would, therefore, be desirable in the future both to examine more thoroughly and in large numbers the relationship between LP, multiple lichen, and vulvar cancer and to find new treatment and follow‐up strategies for pathogenesis.

High Risk of HPV-Related Preneoplastic and Neoplastic Vulvar Lesions in Women Living With HIV

Objective The authors aimed to investigate the epidemiology of human papilloma virus (HPV)-related preneoplastic and neoplastic vulvar lesions in a large cohort of women living with HIV (WLWH). Materials and Methods The authors retrospectively selected 1,796 WLWH who had a gynecological examination, cervical cytology, high-risk (HR-) HPV test, vulvoscopy, and colposcopy with targeted biopsies when necessary between 1987 and 2020 at 2 Italian institutions. Univariable and multivariable regression analyses were carried out to test the association of the anamnestic and clinical data with the development of precancerous and cancerous lesions. Results At baseline, 348 (19.4%) of 1,796 WLWH had genital warts, 30 (1.7%) had vulvar high-grade intraepithelial neoplasia (VHSIL), and 2 (0.1%) had squamous cell carcinoma of the vulva. Among 895 WLWH who had more than 1 year of follow-up, the authors found 40 (4.5%) new cases of VHSIL and 7 (0.8%) cases of vulvar cancer. The cumulative incidence of VHSIL and vulvar cancer was respectively 0.56 and 0.10 per 100 person-years. Risk factors independently associated with the development of vulvar HSIL and cancer included history of injection drug use (p < .01), genital warts at baseline (p < .001), HR-HPV test positivity at diagnosis (p < .001), and severe immunodepression (CD4 cell count <200 cells/mL) at diagnosis (p < .01). Conclusions WLWH are at high risk of vulvar high-grade intraepithelial neoplasia and cancer, especially those with severe immunodepression. A careful inspection of vulva, perineum and anus, possibly with the aid of colposcopy, should become part of the surveillance protocol of HIV-infected women.

New Perspectives in Therapeutic Vaccines for HPV: A Critical Review

Human Papillomavirus is the main cause of cervical cancer, including squamous cell carcinoma of the oropharynx, anus, rectum, penis, vagina, and vulva. In recent years, considerable effort has been made to control HPV-induced diseases using either prophylactic or therapeutic approaches. A critical review of the literature about the therapeutic Human Papillomavirus vaccine was performed to analyze its efficacy in the treatment of female lower genital tract lesions and its possible perspective application in clinical practice. The most important medical databases were consulted, and all papers published from 2000 until 2021 were considered. We retrieved a group of seven papers, reporting the role of anti HPV therapeutic vaccines against the L2 protein in the order of their efficacy and safety in female lower genital tract disease. In addition, the immune response due to vaccine administration was evaluated. The development of therapeutic vaccines represents an interesting challenge for the treatment of HPV infection of the lower genital tract. Literature data underline that the L2 protein may be an interesting and promising target in the development of therapeutic HPV vaccines, but the possible strengths and the unclear longevity of L2 immune responses are factors to be considered before clinical use.

The Complex Interplay between Vaginal Microbiota, HPV Infection, and Immunological Microenvironment in Cervical Intraepithelial Neoplasia: A Literature Review

Background: in recent years, many studies were carried out to explore the role of vaginal microbiota in HPV infections and cervical intraepithelial neoplasia (CIN) progression. The aim of this study was to conduct a review of the literature to analyze the interaction between the vaginal microbiota, the CIN, and the immunological response. Methods: we performed a literature search, considering papers published between November 2015 and September 2021. Results: despite significant evidence suggesting a role of vaginal microbiota in the pathogenesis of HPV-related lesions, some studies still struggle to demonstrate this correlation. However, the vaginal microbiota of HPV-positive women shows an increased diversity, combined with a reduced relative abundance of Lactobacillus spp. and a higher pH. In cervical dysplasia progression, a strong association is found with new bacteria, and with the deregulation of pathways and hyperexpression of cytokines leading to chronic inflammation. Conclusions: in HPV progression, there is a strong correlation between potential biomarkers, such as Sneathia and Delftia found in community state types IV and II, and chronic inflammation with cytokine overexpression. Better analysis of these factors could be of use in the prevention of the progression of the disease and, eventually, in new therapeutic strategies.