Is there a role for platelet rich plasma injection in vulvar lichen sclerosus? A self-controlled pilot study.

BACKGROUND: Owing to the evidence that as many as 30-40% of patients with vulvar lichen sclerosus (VLS) fail to report a remission of symptoms with first-line corticosteroid treatment (TCS), especially as what regards dyspareunia, we aimed to analyze patients' satisfaction following vulvar injection of autologous platelet-rich plasma (PRP). This is intended as an adjunctive treatment, to be used following TCS, and appears to promote tissue repair. It may also possibly have immunomodulatory proprieties. MATERIALS AND METHODS: Patients with VLS were considered eligible for this pilot study if, despite having been treated with a 3-month TCS regimen, they reported a persistence of symptoms. PRP was produced in a referral center using a manual method and a standardized protocol. Each patient received three treatments 4 to 6 weeks apart. RESULTS: A total of 50 patients with a median age of 53 years [IQR 38-59 years] were included in the study. 6 months after the last injection of PRP all patients were either satisfied or very satisfied with the treatment (100%; 95% CI 93-100%). Median NRS scores for itching, burning, dyspareunia and dysuria were significantly reduced (p < 0.05) and FSFI, HADS and SF-12 questionnaires revealed a significant improvement in sexual function, psychological wellbeing and quality of life (p < 0.05). The number of patients reporting the need for maintenance TCS treatment was reduced by 42% (p < 0.001) and an improvement in vulvar elasticity and color was reported in all patients. CONCLUSION: Following standard medical therapy, PRP may be effective not only in improving symptoms, but also in restoring function.

Pediatric vulvar lichen sclerosus: Does it resolve or does it persist after menarche?

BACKGROUND AND OBJECTIVES: Although data regarding the rates of remission and progression of the disease are still scarce, it is generally now acknowledged that pediatric vulvar lichen sclerosus (pVLS) can persist beyond puberty. Recent studies reveal that this condition may persist in as many as 75% of cases. The present study aims to answer the following query: how does pVLS evolve after menarche? METHODS: This observational retrospective study conducted on premenarchal girls diagnosed with pVLS in our institution between 1990 and 2011 describes 31 patients who returned for multidisciplinary clinical evaluation following menarche. RESULTS: The mean follow-up time was 14 years. At the post-menarche clinical examination, patients were classified as follows: 58% were still affected by VLS, 16% presented with a complete remission of disease, and 26% were completely asymptomatic although with persistent clinical signs of VLS. CONCLUSIONS: In our series, pVLS persists following menarche in the majority of patients. These findings suggest the importance of a long-term follow-up even among patients who report resolution of symptoms following menarche.

High-grade vaginal intraepithelial neoplasia and recurrence risk: analysis of an Italian regional referral center series.

PURPOSE: The main aim of this study was to investigate the long-term risk of disease recurrence in women treated for high-grade vaginal intraepithelial neoplasia (HG-VaIN). METHODS: We conducted a retrospective analysis on a cohort of 82 women diagnosed with HG-VaIN between 2010 and 2021 at the "Regional Referral Center for Prevention, Diagnosis and Treatment of HPV-related Genital Disorders", Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. All women underwent either ablative treatment (CO2 laser ablation or electrocoagulation) or cold-knife excision. RESULTS: In our series, the recurrence rate following treatment was 17%. The 5-year cumulative probability of recurrence was 30.4% and the median time to recurrence was 15.5 months. None of the patients progressed to invasive vaginal cancer during follow-up. A concomitant cervical or vulvar intraepithelial lesion was significatively associated with an increased risk of recurrence (p = 0.006). CONCLUSIONS: The results of our study suggest that women with HG-VaIN are at high risk of developing disease recurrence after treatment, especially patients with a concomitant cervical or vulvar intraepithelial lesion. In these women strict monitoring is mandatory to obtain an early identification of recurrence.

Fat Grafting in Vulvar Lichen Sclerosus: Long Term Follow-Up.

OBJECTIVE: The rationale for the use of autologous fat grafting in the treatment of vulvar lichen sclerosus (VLS) consists in reduction of inflammation, regeneration of tissues, volume increase, and pain fiber control. The main outcome of this study was the evaluation of patients' satisfaction after treatment. Secondary outcomes included modifications in symptoms, psychosexual wellbeing, vulvar hydration, and histology after surgery. METHODS: Eligible for this study were women aged 18-85 years with a histological diagnosis of VLS who underwent at least one autologous vulvar fat grafting at the authors' center, between 2010 and 2019. In 2021, all women underwent a clinical reevaluation, comprehensive of vulvoscopy, vulvar biopsy, and handing out of validated questionnaires. RESULTS: Overall, 88.7% of patients declared themselves very satisfied/satisfied with the procedure. All symptoms were improved postsurgery; in particular, the difference was statistically significant for pruritus, burning, and dyspareunia ( p < .05). Sexual function was also improved at time of reevaluation, as were depressive and anxiety symptoms ( p < .05). No cases of vulvar intraepithelial neoplasia or cancer occurred during follow-up and vulvar architecture remained stable, although patients reported a significantly reduced need for topical steroids ( p < .0001). Lastly, in postoperative biopsies, inflammatory infiltrate was stable or reduced, and the distribution of elastic fibers was comparable or restored in most patients. CONCLUSIONS: Patient satisfaction with fat grafting is detectable up to 11 years after surgery, and as such, it may represent a valid therapeutic option in selected cases of VLS.

A clinician's dilemma: what should be communicated to women with oncogenic genital HPV and their partners regarding the risk of oral viral transmission?

Head and neck cancer, the sixth most common cancer worldwide, account for about 1 out of 20 malignant tumors. In recent years a reduction in the incidence of cervical cancer, but a concomitant major increase in the incidence of HPV-mediated oropharyngeal cancer caused by orogenital HPV transmission has been observed. Consequently, in wealthy countries oropharyngeal squamous-cell carcinomas (OPSCC) is now the most frequent HPV-related cancer, having overtaken cervical cancer. Without effective medical interventions, this incidence trend could continue for decades. As no specific precursor lesion has been consistently identified in the oral cavity and oropharynx, HPV vaccination is the logical intervention to successfully counteract also the rising incidence of OPSCCs. However, HPV vaccine uptake remains suboptimal, particularly in males, the population at higher risk of OPSCC. Alternative primary prevention measures, such as modifications in sexual behaviors, could be implemented based on knowledge of individual genital HPV status. Until recently, this information was not available at a population level, but the current gradual shift from cytology (Pap test) to primary HPV testing for cervical cancer screening is revealing the presence of oncogenic viral genotypes in millions of women. In the past, health authorities and professional organizations have not consistently recommended modifications in sexual behaviors to be adopted when a persistent high-risk HPV cervicovaginal infection was identified. However, given the above changing epidemiologic scenario and the recent availability of an immense amount of novel information on genital HPV infection, it is unclear whether patient counseling should change. The right of future partners to be informed of the risk could also be considered. However, any modification of the provided counseling should be based also on the actual likelihood of a beneficial effect on the incidence of HPV-associated oropharyngeal cancers. The risk is on one side to induce unjustified anxiety and provide ineffective instructions, on the other side to miss the opportunity to limit the spread of oral HPV infections. Thus, major health authorities and international gynecologic scientific societies should issue or update specific recommendations, also with the aim of preventing inconsistent health care professionals' behaviors.

Conservative Treatment for Cervical Adenocarcinoma In Situ: Long-Term Results.

OBJECTIVE: This study aimed to evaluate the effectiveness of conservative treatment for cervical adenocarcinoma in situ (AIS). MATERIALS AND METHODS: This is a retrospective study on women with histologically confirmed AIS on cervical loop electrosurgical excision procedure specimen, treated conservatively between 2008 and 2020 in our center, Ospedale Maggiore Policlinico, Milan. The main outcome investigated was the risk of recurrence defined as a subsequent finding of recurrent AIS or invasive adenocarcinoma in a long-term follow-up. The disease-free survival curve was computed using the Kaplan-Meyer method. All patients underwent colposcopy with endocervical curettage and cytology every 6 months for the first 2 years after initial surgery and then annual cytology. RESULTS: Thirty women, aged 26 to 51 years, with histologically proven AIS on excisional specimen with negative margins, negative apex, and negative endocervical curettage were included. The median follow-up was 5.4 years. One woman had a recurrence of AIS after 8 years of follow-up and underwent total hysterectomy. No invasive cervical disease was detected during surveillance. CONCLUSIONS: Women with cervical AIS can be managed conservatively by an excisional procedure, provided that the margins are free and a close and long-term follow-up is guaranteed.

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.

High-risk HPV-positive and -negative high-grade cervical dysplasia: Analysis of 5-year outcomes.

OBJECTIVE: To evaluate the outcomes of high-risk (HR) HPV-positive and -negative women affected by high-grade cervical dysplasia. METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with high-grade cervical dysplasia undergoing conization between 2010 and 2014 were retrieved. All patients included had at least 5 years of follow-up. A propensity-score matching was adopted in order to reduce the presence of confounding factors between groups. Kaplan-Meir and Cox hazard models were used to estimate 5-year outcomes. RESULTS: Overall, data of 2966 women, affected by high-grade cervical dysplasia were reviewed. The study population included 1478 (85%) and 260 (15%) women affected by HR-HPV-positive and HR-HPV-negative high-grade cervical dysplasia. The prevalence of CIN2 and CIN3 among the HR-HPV-positive and -negative cohort was similar (p = 0.315). Patients with HR-HPV-positive high-grade cervical dysplasia were at higher risk of 5-year recurrence (after primary conization) that HR-HPV-negative patients (p < 0.001, log-rank test). Via multivariate analysis, HR-HPV-negative women were at low risk of recurrence (HR: 1.69 (95%CI: 1.05, 4.80); p = 0.018, Cox Hazard model). A propensity-score matched comparison was carried out in order to reduce biases that are related to the retrospective study design. In comparison to HR-HPV-negative patients, thosewith HR-HPV-positive CIN3 was associate with a 8-fold increase in the risk of recurrence (p < 0.001, log-rank test). CONCLUSIONS: HR-HPV-negative high-grade cervical dysplasia is not uncommon, accounting for 15% of our study population. Those patients experience more favorable outcomes than patients with documented HR-HPV infection(s). Further prospective studies are needed to corroborate our data.

Carbon dioxide (CO2) laser ablation of symptomatic vaginal endometriosis: a pilot study.

Deep dyspareunia affects almost half of the women with endometriosis and is associated with vaginal endometriotic lesions. Our pilot study's objective is to assess the feasibility and effectiveness of CO2-laser ablation under colposcopic guidance for the treatment of symptomatic vaginal endometriosis. A non-comparative pilot study has been performed. Only women with histologically proven vaginal endometriosis, who declared the presence of moderate or severe deep dyspareunia, resistant to at least 6 months of conventional hormonal treatment, were deemed eligible for the study. All treatments were performed in an outpatient setting with a colposcopic-guided, hand-directed CO2-laser. Variation in pain symptoms was measured with a 0- to 10-point numerical rating scale (NRS), in sexual functioning with the Female Sexual Function Index (FSFI), in psychological status with the Hospital Anxiety and Depression Scale (HADS), and in quality of life with the Short Form-12 questionnaire (SF-12). Satisfaction with treatment was evaluated according to a five-category scale (very satisfied, satisfied, neither satisfied nor dissatisfied, dissatisfied, very dissatisfied). Nineteen women were enrolled. No complications occurred. At 12-month follow-up, significant improvements were observed in deep dyspareunia and dyschezia scores, in FSFI, HADS, and in the physical component summary scores of SF-12, whereas the mental component score of SF-12 did not vary substantially. Most women (84%) were satisfied with the treatment received. CO2-laser ablation for vaginal endometriosis could represent a valuable alternative option for women with symptomatic lesions, both in terms of amelioration of pain symptoms and improvement in quality of life and sexual function.

The "CIV Classification," a New Proposal for the Architectural Grading of Vulvar Lichen Sclerosus.

OBJECTIVES: The purpose of this cross-sectional study was to prepare a reliable and easy-to-use architectural classification for vulvar lichen sclerosus (VLS) aimed at defining the morphological patterns of this condition. MATERIALS AND METHODS: An expert panel composed by 7 physicians with expertise in clinical care of vulvar conditions outlined the architectural criteria for the definition of VLS severity (phimosis of the clitoris, involvement of the interlabial sulci, narrowing of the vulvar introitus), identifying 5 grades to build up a classification. Thirteen physicians with 2-30 years expertise in vulvar diseases (nonexpert group) were asked to evaluate 3-5 pictures from 137 patients. Each physician individually assigned a grade to each case, according to the previously mentioned criteria. Interrater reliability was analyzed by means of intraclass correlation coefficient (ICC). The reliability concerning the 2 classifications of each rater was analyzed by means of κ statistic. Intraobserver and interobserver reliability in vivo was analyzed by means of κ index. RESULTS: This study provides a new classification of VLS, based on defined anatomical criteria and graded into mutually exclusive progressive classes.The ICC analysis showed a substantial interrater reliability of the classification, ICC = 0.89 (0.87-0.91), both in the expert panel and in the nonexpert group (ICC = 0.92 and 0.87, respectively). An "almost perfect" intraobserver and interobserver reliability was achieved among physicians in vivo (κ = 0.93). CONCLUSIONS: Our classification showed a high reliability. It is easy to use, and it can be applied in clinical practice and eventually, in the evaluation of regenerative and cosmetic surgery.

Recurrence rate after loop electrosurgical excision procedure (LEEP) and laser Conization: A 5-year follow-up study.

OBJECTIVE: Conization aims to remove pre-neoplastic lesions of the uterine cervix. Several techniques for conization have been compared, but evidence regarding the most effective therapeutic option is scant. Here, we aimed to compare the recurrence rate following laser conization and loop electrosurgical excision procedure (LEEP) in patients with high-grade cervical dysplasia (HSIL/CIN2+). METHODS: This is a retrospective multi-institutional study. Medical records of consecutive patients with HSIL/CIN2+ undergoing conization between 2010 and 2014 were retrieved. A propensity-score matching (PSM) was applied in order to reduce allocation bias. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. RESULTS: Overall, 2966 patients had conization over the study period, including 567 (20%) and 2399 (80%) patients having laser conization and LEEP, respectively. Looking at predictors of recurrence, diagnosis of CIN3 (HR:3.80 (95%CI:2.01,7.21); p < 0.001) and HPV persistence (HR:1.81 (95%CI:1.11,2.96); p < 0.001) correlated with an increased risk of recurrence. After applying a PSM we selected 500 patients undergoing laser conization and 1000 undergoing LEEP. Patients undergoing LEEP were at higher risk of having positive surgical margins in comparison to patients undergoing laser conization (11.2% vs. 4.2%). The risk of having persistence of HPV was similar between the two groups (15.0% vs. 11.6%;p = 0.256). Five-year recurrence rate was 8.1% and 4% after LEEP and laser conization, respectively (p = 0.023). HPV persistence was the only factor associated with [5-]year recurrence after both laser conization (p = 0.003) and LEEP (p = 0.001). CONCLUSIONS: HPV persistence is the only factor associated with an increased risk of recurrence after either laser conization or LEEP. Owing to the lack of data regarding obstetrical outcomes, we are not able to assess the best therapeutic option for women with cervical dysplasia.

Medical treatment in the management of deep endometriosis infiltrating the proximal rectum and sigmoid colon: a comprehensive literature review.

A comprehensive literature review was performed to evaluate the effect of various hormonal therapies, in terms of variations of intestinal and pain complaints and of patient satisfaction with treatment, in women with symptomatic, non-severely sub-occlusive endometriosis infiltrating the proximal rectum and sigmoid colon. A MEDLINE search through PubMed from 2000 to 2018 was conducted to identify all original English language articles published on medical treatment for colorectal endometriosis. Additional reports were identified by systematically reviewing reference lists and using the "similar articles" function in PubMed. A total of 420 women with colorectal endometriosis treated with combined oral contraceptives, progestins, gonadotropin releasing-hormone (GnRH) agonists and aromatase inhibitors have been described in eight case series, two retrospective cohort studies and four case reports. Published data consistently suggest that several hormonal medications can control most symptoms associated with intestinal endometriosis, provided the relative bowel lumen stenosis is less than 60%. Patients with irritative-type symptoms appear to respond better than those with constipation. Overall, about two-thirds of women were satisfied with the treatment received, independently of the drug used. Progestins are the compound supported by the largest body of evidence. The addition of aromatase inhibitors or, alternatively, the use of GnRH agonists does not seem to be associated with better outcomes. Long-term treatment with a progestin should be proposed as an alternative to surgery to patients with non-severely sub-occlusive endometriosis infiltrating the proximal rectum and sigmoid colon who are not seeking conception. The final decision should be shared together with the woman, respecting her preferences and priorities.

"Per vaginam" topical use of hormonal drugs in women with symptomatic deep endometriosis: a narrative literature review.

PURPOSE: We aim to provide a comprehensive overview of the role of the vagina as a route for drug delivery and absorption, with a particular focus on the use of vaginal hormonal compounds for the treatment of deep infiltrating symptomatic endometriosis. METHODS: A MEDLINE search through PubMed was performed to identify all published studies in English language on vaginal hormonal treatments for symptomatic endometriosis. RESULTS: Main advantages of the vaginal route include avoidance of the hepatic-first pass metabolic effect, the possibility of using lower therapeutic dosages, and the reduction of side effects compared with the oral administration. Studies on endometriosis treatment mainly focused on the use of vaginal danazol (n = 6) and the contraceptive vaginal ring (n = 2). One pilot study evaluated the efficacy of vaginal anastrozole in women with rectovaginal endometriosis. Most investigations evaluated the vaginal use of hormonal agents in women with deep infiltrating endometriosis/rectovaginal endometriosis. Overall, a substantial amelioration of pelvic pain symptoms associated with endometriosis was observed, particularly of dysmenorrhea. A significant reduction in rectovaginal endometriotic nodule dimensions measured at ultrasound examination was detected by some but not all authors. CONCLUSIONS: The vaginal route represents a scarcely explored modality for drug administration. High local hormonal concentrations might achieve a greater effect on endometriotic lesions compared with alternative routes. Future studies should focus on the use of the vagina for delivering target therapies particularly in patients with deeply infiltrating rectovaginal lesions.

Long-Term Follow-Up Outcomes in Women with In Situ/Microinvasive Adenocarcinoma of the Uterine Cervix Undergoing Conservative Treatment-Cervical Adenocarcinoma Study Group Italian Society of Colposcopy and Cervico-Vaginal Pathology.

OBJECTIVE: The present study aimed to assess long-term follow-up outcomes in women with in situ/microinvasive adenocarcinoma (AC) of the uterine cervix treated conservatively. METHODS: Retrospective multi-institutional study including women with early glandular lesions and 5-year follow-up undergoing fertility-sparing treatment. Independent variables associated with recurrence were evaluated. Logistic regression analysis and Kaplan-Meier survival analysis with Logrank test were performed. RESULTS: Of 269 women diagnosed with in situ/microinvasive AC, 127 participants underwent conservative treatment. During follow-up, recurrences were found in nine women (7.1%). The only factor associated with recurrence during follow-up was positive high-risk Human Papillomavirus (hr-HPV) testing (odds ratio 6.21, confidence interval 1.47-26.08, p = 0.012). HPV positivity in follow-up showed a recurrence rate of 21.7% against 3.8% in patients who were HPV-negative (p = 0.002, Logrank test). Among women with negative high-risk HPV tests in follow-up, recurrences occurred in 20.0% of non-usual-type histology vs. 2.1% of usual-type cases (p = 0.005). CONCLUSION: HPV testing in follow-up is of pivotal importance in women with early glandular lesions undergoing conservative treatment, given its recurrence predictive value. However, women who are high-risk HPV-negative in follow-up with non-usual-type histopathology may represent a sub-population at increased risk of recurrences. Further studies should confirm these findings.

Long term survival of ovarian endometriosis associated clear cell and endometrioid ovarian cancers.

OBJECTIVE: This study aimed to analyze long-term survival of clear cells (CCs) and endometrioid (E) ovarian cancer cases according to presence of endometriosis in the pathologic report. METHODS: This is a retrospective analysis of 47 CC and 66 E ovarian cancer cases observed consecutively at our center between 1990 and 2010.All cases had first surgery at our center or were referred to it for treatment and follow-up.Cases were identified according to the original diagnosis reported in clinical records.All pathologic reports were reviewed, and cases were classified with or without pathologic evidence of endometriosis on the basis of the pathologic report.Follow-up was updated in March 2011. The follow-up median was 147 months (range, 116-171). RESULTS: Endometriosis-associated ovarian cancer cases were more frequently diagnosed at stage I to II than cases without endometriosis: among the 36 endometriosis-associated ovarian cancer cases, 25 (69%) were at stage I or II, and the corresponding value was 35 (46%) of 77 among cases without endometriosis (P = 0.0173).The presence of endometriosis tended to be associated with a higher 10-year survival rate: after taking the potential confounding effect of stage into account, the finding was not statistically significant (hazards ratio, 0.7; 95% confidence interval, 0.3-1.5). CONCLUSIONS: This analysis shows that EA CCs and E ovarian cases are diagnosed at an earlier stage than cases without endometriosis. No clear association emerged between presence of endometriosis and survival.

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.

Correlation Between Colposcopic Patterns and Histological Grade of Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study.

BACKGROUND/AIM: Vaginal intraepithelial neoplasia (VaIN) is a rare human papillomavirus (HPV)- related premalignant condition. VaIN lesions are diagnosed histologically through colposcopy-guided biopsies of suspicious areas, conduced by gynecologists with expertise in lower genital tract diseases. The present study aimed to evaluate the accuracy of colposcopy in the diagnosis of VaIN of any grade. PATIENTS AND METHODS: We conducted a retrospective analysis on a cohort of 149 women diagnosed with low grade (LG)-VaIN (VaIN1) and high grade (HG)-VaIN (VaIN2-3) between 2010 and 2022 at the "Regional Referral Center for Prevention, Diagnosis and Treatment of HPV-related Genital Disorders", Ospedale Maggiore Policlinico, Milan, Italy. All women had been referred to our center for an abnormal Pap smear or as part of routine follow-up of other HPV-related diseases and had undergone a vaginal biopsy under colposcopic guidance. RESULTS: The distribution of the histological grades of VaIN lesions was the following: 62 women (41.6%) were diagnosed with VaIN1, 51 (34.2%) with VaIN2, and 36 (24.2%) with VaIN3. Grade II (major) abnormal colposcopic patterns were recorded in 71 cases (47.7%) and were more commonly observed in women with VaIN3 (80.6%). However, we found a poor and not statistically significant association between colposcopic and histological grade of VaIN. The sensitivity, specificity, positive predictive value, and negative predictive value of colposcopy for histologically confirmed VaIN were 56.3%, 64.5%, 69% and 51.2%, respectively. The overall diagnostic accuracy of colposcopy was 59.7%. CONCLUSION: Colposcopy-guided biopsy plays an important role in the diagnosis of VaIN and in the distinction between low and high-grade lesions. Our data show that major colposcopic abnormalities moderately correlate with HG-VaIN and that grade I colposcopic findings do not exclude HG-VaIN, especially VaIN2. Targeted biopsies of suspicious vaginal areas must be performed in all women with an abnormal Pap smear.

Central Sensitization in Vulvodynia and Endometriosis: What Have We Been Overlooking So Far?

Importance: Women experience more frequent and greater pain than men, although they receive less adequate treatment and are perceived as more anxious than males. Recent clinical research has lead to hypothesize a common etiology for overlapping chronic pain conditions and mood disorders, namely, central sensitization, which originates from an alteration of pain processing pathways in the central nervous system. Objective: The aim of this review was to collect all available evidence regarding the potential role of central sensitization in vulvodynia and endometriosis. Evidence Acquisition: A systematic literature search was performed between July and August 2022 using the electronic database PubMed. The extracted data were summarized using a narrative approach. Results: Ten articles were chosen for the review. Participants' mean age was 39.2 years (SD = 5.1). Among serum markers of central sensitization, nitric oxide levels were greater in women with endometriosis than in controls, whereas brain-derived neurotrophic factor and S100B levels differed among pain conditions with structural anomalies and those without. Functional magnetic resonance imaging showed different resting state networks between patients with endometriosis and controls. In neurophysiology studies, cases had reduced pain thresholds, compared with healthy controls. Lastly, self-reported questionnaires suggested a central component of pain in women with endometriosis-related dyspareunia and associated bladder/pelvic floor tenderness. Conclusions and Relevance: The management of vulvodynia and endometriosis may benefit from a new perspective, which considers their possible central etiology. It is compelling that treatment of pain starts to be considered a therapeutic goal in its own right.

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.

Monitoring the activities of Italian colposcopy clinics before and during the COVID-19 pandemic.

OBJECTIVE: To evaluate the impact of healthcare reorganization during the severe acute respiratory syndrome coronavirus 2 pandemic on Italian colposcopy clinic activities, focusing on cervical excision procedures, follow-ups for conservative management of low-grade lesions, and follow-ups post cervical excision. METHODS: Retrospective study conducted in 14 Italian colposcopy clinics. The number and clinical characteristics of cervical excisions, follow-ups for conservative management of low-grade lesions, and follow-ups after cervical excision were compared between the period March 1, 2019 to February 29, 2020 (pre-pandemic) and March 1, 2020 to February 28, 2021 (pandemic) with a Poisson regression analysis. RESULTS: In the pandemic period, the number of cervical excisions was reduced by 8.8% (95% confidence interval [CI]=-15.6% to -2%; p=0.011). Excisions were less frequently performed in the operating room (-35.1%; 95% CI=-47.6% to -22.6%; p<0.001), the number of patients from spontaneous screening was reduced by -14.0% (95% CI=-23.4% to -4.6%; p=0.003), and the CO2-laser technique was used less frequently (-30%; 95% CI=-45.1% to -15.0%; p<0.001). As compared to the pre-pandemic period, the number of follow-ups for conservative management of low-grade lesions was reduced by -26.7% (95% CI=-39.0% to -14.4%; p<0.001), and the follow-up appointments after cervical excision were reduced by -51.0% (95% CI=-58.1% to -43.9%; p<0.001). CONCLUSION: The most significant impact of the healthcare reorganization during the coronavirus disease 2019 pandemic was on follow-ups after cervical excision. The resumption of disrupted activities should follow a risk-based prioritization, starting from women in follow-up after cervical excision. It is advisable that the trend of performing cervical excision as an outpatient procedure is maintained in the post-pandemic period.