Prevalence of high-grade anal intraepithelial neoplasia in immunocompetent women treated for high-grade cervical intraepithelial neoplasia.

BACKGROUND: The aim of the study was to evaluate the prevalence of high-grade anal intraepithelial neoplasia (AIN2-3) among immunocompetent women treated for high-grade cervical intraepithelial neoplasia (CIN2-3). Such knowledge is strongly needed to establish whether a screening program should be recommended in this group of patients. METHODS: This prospective study included a cohort of consecutive women with no known causes of immunosuppression treated with LEEP (loop electrosurgical excision procedure) for a histopathological diagnosis of CIN2-3 in our center between 2019 and 2021. Following the procedure, all patients were invited to undergo anal cytology and anal high-risk HPV-DNA testing (aHPV-DNA). In cases in which one or both tests resulted positive, a high-resolution anoscopy with a biopsy of suspicious lesions was performed. All women also completed a questionnaire on sexual habits. RESULTS: At total of 100 women were enrolled in the study. Among these, eight patients had a concomitant or past diagnosis of anogenital warts, while one patient had received a previous diagnosis of high-grade vaginal intraepithelial neoplasia. Anal Pap smears were positive for low-grade lesions in three patients, while 73 women tested positive for aHPV-DNA. Histological examinations revealed the presence of AIN2-3 lesions in four patients (6.5%; 95% C.I., 1.8 to 15.7%), who subsequently underwent excisional treatment. CONCLUSIONS: Women with a history of high-grade cervical intraepithelial neoplasia have an intermediate risk of developing high-grade anal intraepithelial neoplasia. Future studies are needed in order to assess an ideal screening approach for this condition.

Should attention be paid to the cone depth in the fully visible transformation zone? Retrospective analysis of 517 patients with cervical intraepithelial neoplasia grade 3.

OBJECTIVE: The predictors of positive endocervical margin (EM) and a cone-depth cutoff value are not established in the fully visible transformation zone (TZ). The present study aimed to assess the independent variables associated with positive EM in women with high-grade cervical intraepithelial neoplasia (CIN) and fully visible TZ. METHODS: The current investigation was a retrospective study including women with fully visible TZ and CIN 3 cone histology between 2014 and 2019. The sample was divided into women with positive versus those with negative EM. Univariate and multivariate analyses were performed. Finally, receiver operating characteristic curve analysis was also used. RESULTS: A total of 123 of 517 women (23.8%) showed positive EM at conization. Multivariate analysis found a positive association with type 2 TZ (odds ratio [OR], 2.17 [95% confidence interval (CI), 1.19-3.94]) and lesion extension ≥2 cervical quadrants (OR, 35.57 [95% CI, 17.96-70.45]). Cone depth was inversely related to positive EM (OR, 0.71 [95% CI, 0.63-0.80]). In women with type 2 TZ and lesion extension ≥2 cervical quadrants, the cutoff value was achieved at 8-mm cone depth (area under the curve, 0.79 [95% CI, 0.67-0.90]). CONCLUSION: In women with high-grade CIN and fully visible TZ undergoing conization, the lesion extension and the TZ subtype (1 or 2) should be considered. A no less than 9-mm cone depth provided a fair predictive value in achieving free EM.

Periodontitis, female fertility and conception (Review).

Periodontal disease (PD) has been shown to increase the risk of preterm birth, preeclampsia and low birth weight. These observations have suggested that PD may also affect the early phase of pregnancy, including conception. The present study aimed to evaluate whether an association exists between oral health status and the chance of clinical pregnancy, according to the currently published literature, by performing a systematic review. The PubMed and EMBASE databases were searched from their start dates to October 2021 using the following keywords: 'Infertility' OR 'conception' OR 'pre-pregnancy' OR 'time-to-pregnancy' AND 'periodontitis' OR 'periodontal disease' OR 'dental infection' OR 'gingivitis' OR 'odontogenic infection' (limits: Full article, English, Human). A total of 6 papers reporting observational information on PD and spontaneous (4 studies) or medically induced conception (2 studies) were retrieved. As such, there were limited studies with different designs (randomized controlled trials and observational studies) and different settings. Moreover, in the selected studies, the ethnicity of the women was heterogeneous. According to the limited published literature, oral health might affect fertility in women. However, only results from prospective randomized trials, comparing PD treatment vs. no treatment in women seeking pregnancy, may clarify the real effectiveness of treatment in improving the conception rate.

Sleep disturbances, fatigue and psychological health in women with endometriosis: a matched pair case-control study.

RESEARCH QUESTION: What are the associations between endometriosis, pelvic pain symptoms, fatigue and sleep? Psychological health and quality of life in endometriosis patients with good versus bad quality of sleep were also examined. DESIGN: This matched pair case-control study included 123 consecutive endometriosis patients and 123 women without a history of endometriosis (matched to patients for age and body mass index). Endometriosis-related pelvic pain severity was rated on a 0-10 numerical rating scale. Fatigue was measured on a 1-5 Likert scale. Women also completed a set of self-report questionnaires for assessing sleep disturbances (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Insomnia Severity Index), psychological health (Hospital Anxiety and Depression Scale) and quality of life (Short Form-12). RESULTS: Painful endometriosis had an impact on fatigue (P = 0.006; η2p = 0.041) and sleep (P < 0.001; η2p = 0.051). Women with painful endometriosis reported significantly greater fatigue, poorer quality of sleep, higher daytime sleepiness and more severe insomnia than women without significant pain symptoms and controls. Poorer quality of sleep among endometriosis patients was associated with greater fatigue (P < 0.001; η2p = 0.130), poorer psychological health (P < 0.001; η2p = 0.135), and lower quality of life (P < 0.001; η2p = 0.240). CONCLUSIONS: Pelvic pain (rather than endometriosis in itself) is associated with fatigue and sleep disturbances, with poor sleep having a detrimental impact on women's psychological health and quality of life.

Trend of HPV 16/18 Genotypes in Cervical Intraepithelial Neoplasia Grade 3: Data for 2007-2018.

AIM: In the post-vaccination era, the starting age and time intervals of cervical screening could change (older age and longer screening intervals). This scenario may be achieved by significantly reducing human papillomavirus (HPV) 16/18 prevalence (genotypes included in the current vaccines). In this regard, assessing the trend over time of these HPV infections in high-grade cervical lesions can provide information on the objective. The present study aimed to evaluate the trend of HPV 16/18 over the years 2007-2018 in women with cervical intraepithelial neoplasia (CIN) grade 3. METHODS: This is a retrospective multi-institutional study including HPV genotyped and unvaccinated women under 30 with CIN3. The sample was divided into the following periods: 2007-2010, 2011-2014, 2015-2018. HPV genotypes were grouped in genotypes 16/18, genotypes 31/33/35/52/58/67 (genetically related to HPV16), genotypes 39/45/59/68/70 (genetically related to HPV18), genotypes 31/33/45/52/58 (high-risk types included in the nonavalent vaccine), possibly carcinogenic HPV (genotypes 26/30/53/67/70/73/82/85), low-risk HPV (genotypes 6/11/40/42/43/44/54/55/61). The trend between periods and HPV genotypes was measured using the Cochran-Armitage test for trend. RESULTS: The final analysis included 474 participants. HPV 16/18 prevalence decreased significantly over the years (77.8% vs 68.9% vs 66.0%, respectively, Ptrend=0.027). Possibly carcinogenic HPV (genotypes 26/30/53/67/70/73/82/85) showed a significant negative prevalence trend over time (4.9% vs 1.1% vs 1.3%, respectively, Ptrend=0.046). Finally, there was a significant positive trend over the years for high-risk HPV genotypes 31/33/45/52/58 in women under 25 (9.9% vs 17.0% vs 24.0%, respectively, Ptrend=0.048). CONCLUSION: The prevalence of CIN3 lesions related to HPV 16/18 genotypes decreased over time from 2007 to 2018. These data highlight a herd effect of the HPV vaccine. However, fifteen years after HPV vaccine introduction, we are still a long way from herd immunity. The increase in high-risk types 31/33/45/52/58 will need to be reassessed when the nonavalent vaccine impact will be more reliable.

Age-related distribution of uncommon HPV genotypes in cervical intraepithelial neoplasia grade 3.

AIM: Cervical cancer prevention guidelines include Human Papillomavirus (HPV) test, cytology, and HPV-16/18 typing for triage to determine the risk of cervical intraepithelial neoplasia (CIN) grade 3 as the best proxy of cervical cancer risk. In doing that, they do not consider how age can modify the type-specific risk of CIN3. The present study aimed to evaluate the age-related distribution of HPV genotypes affecting the risk-assessment in cervical cancer screening programs: non-screening-type-HPV and non-HPV-16/18 in unvaccinated women with CIN3. METHODS: Retrospective multi-institutional study, including HPV genotyped women with CIN3 on cone histology treated between 2014 and 2019. The sample was divided into three categories of age: <30, 30-44, ≥45. HPV genotypes were grouped in non-screening-type-HPV (not-including genotypes 16/18/31/33/35/39/45/51/52/56/58/59/66/68) and non-HPV-16/18. Associations and trends between different age-groups and HPV genotypes were measured. RESULTS: 1332 women were analyzed. Non-screening-type-HPV CIN3 were 73 (5.5%). Non-HPV-16/18 were found in 417 participants (31.3%). Women over 45 associated with non-screening-type HPV [odds ratio (OR) = 1.87, 95% confidence interval (CI) 1.07-3.25; p = 0.027]. Non-screening-type-HPV prevalence increased significantly with age (3.9% vs 5.1% vs 9.0%, p = 0.016). Women under 30 showed a lower rate of non-HPV-16/18 (OR = 0.65, 95% CI 0.47-0.89; p = 0.007). There was a positive trend with age of non-HPV-16/18 CIN3 (23.6% vs 32.1% vs 38.0%, p = 0.0004). CONCLUSION: The proportion of CIN3 lesions unrelated to genotypes detected by primary screening tests increased with age. This implies that age probably modifies the risk of CIN3 and possibly of cancer associated with HPV types. The risk-based recommendation should take into consideration age to define the management of HPV positive women.

Endometriosis and inflammatory bowel disease: A systematic review of the literature.

The potential link between endometriosis and Inflammatory Bowel Disease (IBD) has been investigated over the last twenty years. Endometriosis shares with IBD features and symptoms so to become a significant diagnostic challenge, resulting in a delayed or indeterminate diagnosis. We conducted a systematic review to summarize the available data in literature on the co-diagnosis of IBD and endometriosis. A systematic literature search was performed using the electronic databases MEDLINE and EMBASE from 1990 to November 2019, using the search terms: inflammatory bowel disease OR ulcerative colitis OR Crohn's disease AND endometriosis. We selected 23 articles: 15 case-report, 3 clinical series, 3 case-control studies, 1 cross-sectional study and 1 cohort study. All the epidemiological studies included in this review reported a positive association between endometriosis and IBD. Meta-analysis was not possible because, due to study design and type of patients included, there were no comparable groups to analyze. In epidemiological studies with a control group, the proportion of IBD in patients with endometriosis varied from 2 to 3.4 %, compared to 0-1 % of the control group. A large nationwide Danish cohort study reported a 50 % increase in the risk of IBD in women with endometriosis in comparison with women in the general population. In a large Danish cohort study women with endometriosis had an increased risk of CD and UC with a standardized incidence ratio of 1.5 (95 % CI 1.3-1.7) and 1.6 (95 % CI 1.3-2.0) respectively. Several studies do not provide information on the temporal sequence of endometriosis and IBD and therefore a clear analysis of a cause-effect association between these two pathologies is lacking. The high number of case-reports in the literature highlights how the diagnosis can be challenged, as endometriosis can be masquerading as IBD or vice versa or be present within the same patient. Further research is needed to better understand the temporal association between endometriosis and IBD, which could be useful to correct evaluation and improve the management of these patients.

Pregnancy-associated cancers: frequency and temporal trends in Italy.

OBJECTIVE: Limited data are available on the frequency and time trends of pregnancy-associated cancers, particularly from Southern European countries. The aim of this study was to analyze the frequency and time trends of pregnancy-associated cancer in Italy. METHODS: This was a population-based linkage study using the regional hospital discharge forms database of four Italian regions with more than 17 million inhabitants. All resident women with a hospital discharge form reporting a birth or abortion in the time period under consideration were identified. The time period of the study was 2003-2015 for the Piemonte and Puglia region, 2006-2015 for the Tuscany region, and 2005-2015 for the Veneto region. Risk of developing a pregnancy-associated cancer was calculated as the ratio of the number of pregnancy-related cancers to the total number of pregnancies. RESULTS: A total of 2 297 648 pregnancies were identified. Overall, the pregnancy-associated cancer frequency was 134.8 per 100 000 pregnancies: the frequency ranged from 127.1 in Puglia to 157.3 in Tuscany. The frequency for 100 000 pregnancies was 66.4 in women aged <30 years; the risk increased with age, with a frequency of 275.6 among women aged 40+ years. Approximately two-thirds of cancers were associated with pregnancies resulting in a delivery and one-third with pregnancies resulting in a termination of pregnancy or spontaneous pregnancy loss. No clear trend emerged in the risk of pregnancy-associated cancer per 100 000 pregnancies and calendar year. CONCLUSION: No clear time trend was observed in the frequency of pregnancy-associated cancers in Italy during the last 10 years, the rates being 104, 164, and 130 per 100 000 pregnancies, respectively, in 2003, 2010, and 2015.

25-Hydroxyvitamin D Serum Levels and Endometriosis: Results of a Case-Control Study.

The immunomodulatory, anti-inflammatory, and antiproliferative properties of vitamin D have laid the basis for a possible function of this prohormone in the pathogenesis of endometriosis. The aim of this case-control study was to investigate vitamin D status, by measuring 25-hydroxyvitamin D [25(OH)D] serum levels, in women with and without endometriosis. Only Italian women of Caucasian origin aged between 18 and 45 years were deemed eligible. Enrollment was limited to the period October to May. Cases and controls were matched for month of recruitment and secondarily for age and parity. Overall, 434 women were enrolled (endometriosis n = 217; controls n = 217). The group of cases included 127 women with ovarian endometrioma and 90 patients with deep endometriosis. Mean (standard deviation) levels of 25(OH)D in women with and without endometriosis were 17.9 (7.0) ng/mL and 18.4 (7.6) ng/mL, respectively ( P = .46). Analyzing the two endometriosis subgroups separately, no statistically significant differences emerged (18.7 [7.4] ng/mL in deep endometriosis group vs 17.3 [6.6] ng/mL in women with ovarian endometrioma; P = .14). Comparing the subgroup of women with deep endometriosis with paired controls, no differences occurred (18.7 [7.4] ng/mL vs 18.5 [7.7] ng/mL, P = .80). Similar data emerged when performing the same analysis for ovarian endometriomas (17.4 [6.6] ng/mL vs 18.3 [7.6] ng/mL, P = .23). The results of the present case-control study do not support an association between serum vitamin D levels and different phenotypes of endometriosis.

The limited oncogenic potential of unilocular adnexal cysts: A systematic review and meta-analysis.

The reported frequency of malignant diseases in unilocular cysts varies in different studies, giving conflicting results. To quantify the risk of malignancies among echoic and anechoic unilocular adnexal cysts, in premenopausal and postmenopausal women, we performed a PubMed/MEDLINE search of papers published in English evaluating the histopathological diagnoses of removed ovarian cysts diagnosed as simple unilocular cysts at pre-operative ultrasound examination. From 34 selected publications, we extracted data on ovarian malignancy in the total series, and separately for premenopausal and postmenopausal women, and women with cysts < 5 cm and ≥5 cm in diameter. Of the 2177 surgically removed lesions classified as unilocular cysts on pre-operative ultrasound, 24 (1.1%; 95% CI: 0.74-1.66) were malignant (among these 12 had borderline malignancy: 0.6%). The rates were lower for premenopausal women (6/987, 0.6%) than postmenopausal ones (12/372, 3.2%). Of the 2290 surgically removed lesions classified as anechoic unilocular cysts on ultrasound, 20 (0.9%; 95% CI: 0.57-1.35) were malignant (among these 8 had borderline malignancy: 0.3%). The rates were lower for premenopausal women (3/907, 0.3%) than postmenopausal ones (13/681, 1.9%) (Pearson chi-square P = 0.002). When we performed meta-analysis selecting studies including only anechoic unilocular cysts published after 2000 and with 100 or more patients, the estimate was 0.5 (95% CI 0.1-1.2) with no heterogeneity (heterogeneity chi-square P = 0.175). The oncogenic risk of unilocular adnexal cysts is low, suggesting that the final choice about surgical treatment of these cysts should be based on the combination of each patient's overall risk profile as well as personal priorities.

Vitamin D and benign gynaecological diseases: a critical analysis of the current evidence.

Vitamin D is a fat-soluble pro-hormone that plays an important role in bone homeostasis; beside this principal function, vitamin D promotes modulation of cell growth, neuromuscular and immune function, and reduction of inflammation. In addition, several in vitro and in vivo studies have demonstrated that vitamin D deficiency could increase the risk of cancer, autoimmune and cardiovascular diseases. Moreover, vitamin D plays also an important role in female reproduction, because vitamin D receptors are expressed in ovarian tissue, endometrium, fallopian epithelial cells as well as in decidua and placenta. We aimed to review the most updated evidence, which suggests a link between vitamin D metabolism and the development of some gynaecological diseases, such as endometriosis, uterine fibroids and polycystic ovary syndrome.

The effect of macrobiotic Ma-Pi 2 diet on systemic inflammation in patients with type 2 diabetes: a post hoc analysis of the MADIAB trial.

INTRODUCTION: Current guidelines for the management of type 2 diabetes (T2D) emphasize diet as essential therapy. However, the effect of diet on systemic inflammation remains unclear. We investigated the effects of consuming a macrobiotic Ma-Pi 2 diet versus a standard recommended diet (control diet) on markers of inflammation in patients with T2D. METHODS: This was a post hoc analysis of the MADIAB trial, a 21-day randomized controlled trial conducted in 51 patients (25 males and 26 females) with T2D. Patients were randomized 1:1 to the Ma-Pi 2 macrobiotic diet or a control diet based on dietary guidelines for T2D. Biological antioxidant potential of plasma and circulating levels of high-sensitivity C reactive protein, interleukin-6, tumor necrosis factor-α, and insulin-like growth factor-1 were assessed. RESULTS: After 21 days on the Ma-Pi 2 or control diet, markers of inflammation were reduced in both groups. The antioxidant potential of plasma improved significantly in the Ma-Pi group. A significant reduction in insulin growth factor-1 was observed in the Ma-Pi group versus control group (p<0.001). CONCLUSIONS: Findings of this post hoc analysis demonstrated that the Ma-Pi 2 diet is a safe dietary strategy to reduce levels of the markers of insulin resistance and inflammation, compared with baseline values, in the short term. Furthermore, the Ma-Pi 2 diet was superior to the control diet in reducing insulin growth factor-1 and may be beneficial for patients with T2D. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN10467793.

The effect of the macrobiotic Ma-Pi 2 diet vs. the recommended diet in the management of type 2 diabetes: the randomized controlled MADIAB trial.

BACKGROUND: Diet is an important component of type 2 diabetes therapy. Low adherence to current therapeutic diets points out to the need for alternative dietary approaches. This study evaluated the effect of a different dietary approach, the macrobiotic Ma-Pi 2 diet, and compared it with standard diets recommended for patients with type 2 diabetes. METHODS: A randomized, controlled, open-label, 21-day trial was undertaken in patients with type 2 diabetes comparing the Ma-Pi 2 diet with standard (control) diet recommended by professional societies for treatment of type 2 diabetes. Changes in fasting blood glucose (FBG) and post-prandial blood glucose (PPBG) were primary outcomes. HbA1c, insulin resistance (IR), lipid panel and anthropometrics were secondary outcomes. RESULTS: After correcting for age, gender, BMI at baseline, and physical activity, there was a significantly greater reduction in the primary outcomes FBG (95% CI: 1.79; 13.46) and PPBG (95% CI: 5.39; 31.44) in those patients receiving the Ma-Pi 2 diet compared with those receiving the control diet. Statistically significantly greater reductions in the secondary outcomes, HbA1c (95% CI: 1.28; 5.46), insulin resistance, total cholesterol, LDL cholesterol and LDL/HDL ratio, BMI, body weight, waist and hip circumference were also found in the Ma-Pi 2 diet group compared with the control diet group. The latter group had a significantly greater reduction of triglycerides compared with the Ma-Pi 2 diet group. CONCLUSIONS: Intervention with a short-term Ma-Pi 2 diet resulted in significantly greater improvements in metabolic control in patients with type 2 diabetes compared with intervention with standard diets recommended for these patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10467793.