Anal high-grade intraepithelial neoplasia and cancer in women living with HIV and HIV-negative women with other risk factors.

OBJECTIVE: To determine the prevalence and the risk factors for anal high-grade intraepithelial neoplasia and anal cancer (HSIL+) in women living with HIV (WLWHIV), and to compare them to HIV-negative women with other risk factors. DESIGN: Prospective cohort study. METHODS: WLWHIV and HIV-negative women with other risk factors were included. Screening for anal HSIL+ using anal cytology and HPV testing was performed. A high-resolution anoscopy with directed biopsy was also performed in patients with an abnormal cytology result or a positive HPV testing for high-risk (HR) genotypes, and in those with anal symptoms. RESULTS: The period prevalence of anal HR-HPV infection and histological HSIL was 57.9% and 10.9% among WLWHIV, and 60.8% and 9.2% among HIV-negative women. The prevalence of anal HPV 18 infection was higher in WLWHIV. The risk factors for anal HSIL+ in WLWHIV included anal HPV 16, other HR genotypes and low-risk genotypes infection, as well as a history of vulvar HSIL+. In HIV-negative women, the risk factors included anal HPV 16 infection, history of anogenital warts and of vulvar HSIL+, and immunosuppressive treatment. CONCLUSIONS: A high prevalence of anal HPV infection and HSIL was observed in WLWHIV and women with other risk factors. Both groups share anal HPV 16 infection and history of vulvar HSIL+ as risk factors for the development of anal HSIL+. Genotyping for anal HPV 16 may help identify women at higher risk of anal cancer.

Menopause in adult women with human papillomavirus: health-related quality of life and determinants.

OBJECTIVE: Human papillomavirus (HPV) infection and menopause entail a considerable impairment in health-related quality of life (HRQoL). The objective of the present study was to analyze the impact of the menopause status on HRQoL in women with HPV infection. METHODS: A cross-sectional, nationwide, multicenter sample of women with HPV infection was conducted throughout clinics of gynecology representative of the Spanish population with regard to age, geographic density, and autonomous regions. Demographic and clinical characteristics and the specific HPV-QoL questionnaire score with its domains were compared according to reproductive status: premenopausal and peri-/postmenopausal. Correlation with other validated patient-reported outcomes measurements was also tested, including General Health Questionnaire-12 (GHQ-12), Female Sexual Function Index (FSFI), and Hospital Anxiety and Depression Scale (HADS). RESULTS: A sample of 1,016 noninstitutionalized women, aged 18-80 y, was recorded, 191 (18.8%) peri-/postmenopausal and 825 (81.2%) premenopausal. Total HPV-QoL scoring was significantly lower in peri-/postmenopausal (38.8, 95% CI [35.2-42.4]) compared to premenopausal (46.4, 95% CI [45.0-47.8]) women, and also in every domain of the scale (P < 0.05), except in social well-being and health domains, with a small effect size of 0.39. In women with sexual dysfunction according to FSFI, adjusted total scoring and domains sexuality, general well-being, and psychological well-being scored significantly higher in premenopause women (P < 0.01), although the magnitude of differences were of small to moderate size. CONCLUSIONS: HRQoL was impaired during menopause in women with HPV infection according to HPV-QoL questionnaire. The sexuality domain was the most differentiating dimension between these populations.

Population-based norms for the human papillomavirus-quality of life (HPV-QoL) questionnaire: A cross-sectional multicenter study.

INTRODUCTION: Human papillomavirus (HPV) diagnosis has a considerable emotional and psychological impact on women. To evaluate the impairment this infection leads to regarding quality of life (QoL), several scales have been suggested, such as the human-papillomavirus-quality-of-life (HPV-QoL) questionnaire. This has been validated for the Spanish population and measures the impact of HPV on health-related-quality-of-life (HR-QoL). However, normative values are yet to be developed. Thus, the objective was to describe the population-based norms of the HPV-QoL for Spanish women aged 25-65 years and to test the questionnaire's construct validity. MATERIAL AND METHODS: This was a cross-sectional nationwide multicenter study. Women from outpatient clinics in Spain aged 25-65 years, with a diagnosis of past or active HPV infection were recruited. The central tendency, dispersion, and percentiles were calculated for the total score and its dimensions for each age group. Construct validity was tested by analyzing age groups and their correlations with other related scales (12-Item General Health Questionnaire [GHQ-12], Female Sexual Function Index [FSFI], and Hospital Anxiety and Depression Scale [HADS]). RESULTS: A total of 1352 women were included in the study. The norms showed moderate and significant coefficients of correlation with other related scales. Significant differences between age strata groups were found according to educational level, sexual dysfunction, sexual activity, mental deterioration, and severity of anxiety and depression symptoms (p < 0.001 in all cases). The total score differed significantly between the groups (p = 0.006). Significant differences in the contagiousness, health, and sexuality dimensions (p < 0.05) were found among the groups. It was seen that HPV infection impaired women's QoL. Dimensions within all test age groups (p < 0.001 in all cases) were significantly different, with the health dimension being the highest contributor to women's QoL impairment, whereas social well-being was the main determinant of QoL. CONCLUSIONS: Population-based norms for the novel HPV-QoL questionnaire showed adequate validity and could be a useful tool for assessing the impact of QoL among women with HPV in Spain.

Patterns of First Recurrence and Oncological Outcomes in Locally Advanced Cervical Cancer Patients: Does Surgical Staging Play a Role?

BACKGROUND: We aimed to determine whether surgical aortic staging by minimally invasive paraaortic lymphadenectomy (PALND) affects the pattern of first recurrence and survival in treated locally advanced cervical cancer (LACC) patients when compared to patients staged by imaging (noPALND). METHODS: This study was a multicenter observational retrospective cohort study of patients with LACC treated at tertiary care hospitals throughout Spain. The inclusion criteria were histological diagnosis of squamous carcinoma, adenosquamous carcinoma, and/or adenocarcinoma; FIGO stages IB2, IIA2-IVA (FIGO 2009); and planned treatment with primary chemoradiotherapy between 2000 and 2016. Propensity score matching (PSM) was performed before the analysis. RESULTS: After PSM and sample replacement, 1092 patients were included for analysis (noPALND n = 546, PALND n = 546). Twenty-one percent of patients recurred during follow-up, with the PALND group having almost double the recurrences of the noPALND group (noPALND: 15.0%, PALND: 28.0%, p < 0.001). Nodal (regional) recurrences were more frequently observed in PALND patients (noPALND:2.4%, PALND: 11.2%, p < 0.001). Among those who recurred regionally, 57.1% recurred at the pelvic nodes, 37.1% recurred at the aortic nodes, and 5.7% recurred simultaneously at both the pelvic and aortic nodes. Patients who underwent a staging PALND were more frequently diagnosed with a distant recurrence (noPALND: 7.0%, PALND: 15.6%, p < 0.001). PALND patients presented poorer overall, cancer-specific, and disease-free survival when compared to patients in the noPALND group. CONCLUSION: After treatment, surgically staged patients with LACC recurred more frequently and showed worse survival rates.

Procalcitonin and C-reactive protein as early markers of anastomotic leakage in intestinal resections for advanced ovarian cancer (EDMOCS).

INTRODUCTION: Serum levels of procalcitonin and C-reactive protein (CRP) have been used to predict anastomotic leakage after colorectal surgery, but information is scarce in advanced ovarian cancer (AOC) surgery with bowel resection. This study aimed to assess the predictive value of procalcitonin and CRP in detecting anastomotic leakage after AOC surgery with bowel resection. The study also aimed to determine the optimal postoperative reference values and the best day for evaluating these markers. MATERIAL AND METHODS: This prospective, observational and multicentric trial included 92 patients with AOC undergoing debulking surgery with bowel resection between 2017 and 2020 in 10 reference hospitals in Spain. Procalcitonin and CRP levels were measured at baseline and on postoperative days 1-6. Receiver operating characteristic analysis was performed to evaluate the predictive value of procalcitonin and CRP at each postoperative day. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Anastomotic leakage was detected in six patients (6.5%). Procalcitonin and CRP values were consistently higher in patients with anastomotic leakage at all postoperative days. The maximum area under the curve (AUC) for procalcitonin was observed at postoperative day 1 (AUC = 0.823) with a cutoff value of 3.8 ng/mL (83.3% sensitivity, 81.3% specificity). For CRP, the maximum AUC was found at postoperative day 3 (AUC = 0.833) with a cutoff level of 30.5 mg/dL (100% sensitivity, 80.4% specificity). CONCLUSIONS: Procalcitonin and C-reactive protein are potential biomarkers for early detection of anastomotic leakage after ovarian cancer surgery with bowel resection. Further prospective studies with a larger sample size are needed to confirm these findings.

Can the microcystic, elongated and fragmented pattern of invasion influence the evaluation of the depth of myometrial invasion in low-grade endometrioid endometrial cancer using imaging techniques?

Objectives: The microcystic, elongated and fragmented pattern of invasion can be associated with an underestimation of the depth of myometrial invasion by imaging techniques. We aimed to evaluate the influence of microcystic, elongated and fragmented pattern of invasion in the diagnostic performance of transvaginal ultrasound scan and magnetic resonance imaging for the prediction of the depth of myometrial invasion in low-grade endometrioid endometrial carcinomas. Methods: Prospective and consecutive study including all low-grade (G1-G2) endometrioid endometrial carcinomas diagnosed between October 2013 and July 2018 in a tertiary hospital. Preoperative staging was performed with transvaginal ultrasound scan and/or magnetic resonance imaging followed by surgical staging. Final histology was considered as the reference standard. Sensitivity, specificity and diagnostic accuracy for the prediction of depth of myometrial invasion was calculated for both imaging techniques. The STARD 2015 guidelines were used. Results: A total of 136 patients were consecutively included. Transvaginal ultrasound scan was performed in 132 patients and magnetic resonance imaging in 119 patients. The diagnostic accuracy of transvaginal ultrasound scan for the prediction of depth of myometrial invasion in the microcystic, elongated and fragmented negative group (82% (95% confidence interval = 73-88)) was higher compared to the microcystic, elongated and fragmented positive group (61% (95% confidence interval = 36-83)). The diagnostic accuracy of magnetic resonance imaging was also higher in the microcystic, elongated and fragmented negative group (80% (95% confidence interval = 71-87)) compared to the microcystic, elongated and fragmented positive (47% (95% confidence interval = 21-73)). Conclusions: In low-grade endometrioid endometrial carcinomas with a positive microcystic, elongated and fragmented pattern of invasion, the evaluation of the depth of myometrial invasion using transvaginal ultrasound scan and magnetic resonance imaging may be underestimated.

A combination of molecular and clinical parameters provides a new strategy for high-grade serous ovarian cancer patient management.

BACKGROUND: High-grade serous carcinoma (HGSC) is the most common and deadly subtype of ovarian cancer. Although most patients will initially respond to first-line treatment with a combination of surgery and platinum-based chemotherapy, up to a quarter will be resistant to treatment. We aimed to identify a new strategy to improve HGSC patient management at the time of cancer diagnosis (HGSC-1LTR). METHODS: A total of 109 ready-available formalin-fixed paraffin-embedded HGSC tissues obtained at the time of HGSC diagnosis were selected for proteomic analysis. Clinical data, treatment approach and outcomes were collected for all patients. An initial discovery cohort (n = 21) were divided into chemoresistant and chemosensitive groups and evaluated using discovery mass-spectrometry (MS)-based proteomics. Proteins showing differential abundance between groups were verified in a verification cohort (n = 88) using targeted MS-based proteomics. A logistic regression model was used to select those proteins able to correctly classify patients into chemoresistant and chemosensitive. The classification performance of the protein and clinical data combinations were assessed through the generation of receiver operating characteristic (ROC) curves. RESULTS: Using the HGSC-1LTR strategy we have identified a molecular signature (TKT, LAMC1 and FUCO) that combined with ready available clinical data (patients' age, menopausal status, serum CA125 levels, and treatment approach) is able to predict patient response to first-line treatment with an AUC: 0.82 (95% CI 0.72-0.92). CONCLUSIONS: We have established a new strategy that combines molecular and clinical parameters to predict the response to first-line treatment in HGSC patients (HGSC-1LTR). This strategy can allow the identification of chemoresistance at the time of diagnosis providing the optimization of therapeutic decision making and the evaluation of alternative treatment strategies. Thus, advancing towards the improvement of patient outcome and the individualization of HGSC patients' care.

Surgical Outcomes of Laparoscopic Pelvic Lymph Node Debulking during Staging Aortic Lymphadenectomy in Locally Advanced Cervical Cancer: A Multicenter Study.

BACKGROUND: Few studies have evaluated laparoscopic pelvic lymph node (PLN) debulking during staging aortic lymphadenectomy in locally advanced cervical cancer (LACC). It allows us to know the lymph node status and facilitates the action of chemoradiotherapy (CRT) by reducing tumor burden. We evaluated its feasibility and compared the perioperative morbidity and the time to CRT with a control group. METHODS: This was a multicenter retrospective study of patients with LACC FIGO stage IIIC1r who were recipients of CRT. We compared two cohorts: group 1, which consisted of 164 patients with surgical staging by laparoscopic aortic lymphadenectomy and PLN debulking, and group 2, which consisted of 111 patients with aortic lymphadenectomy alone. RESULTS: Excision of the bulky nodes was possible in all patients in group 1 except for one. Surgery lasted a median of 82 min longer in group 1 but there was no greater intraoperative bleeding or increased hospital stay. There were no significant differences in intraoperative or postoperative complications between the groups. A significantly shorter time from surgery to the start of RT was observed in group 1. CONCLUSIONS: It is feasible to perform laparoscopic PLN debulking in the same procedure as the staging aortic lymphadenectomy in LACC without increasing surgical or postoperative complications and without delaying the start of CRT compared to single aortic lymphadenectomy.

Adjuvant therapy in early-stage cervical cancer after radical hysterectomy: are we overtreating our patients? A meta-analysis.

OBJECTIVE: There is a gap in knowledge regarding the ideal management of patients with early-stage cervical cancer and intermediate-risk features. Here, we present a meta-analysis of the published literature on oncological outcomes in these patients and determine trends in postoperative management. METHODS: MEDLINE and PubMed were used for literature searches. The inclusion criteria were: English language articles including ≥ 10 patients, patients who underwent radical hysterectomy, nodes negative, studies reporting oncological outcomes and complications treatment-related and compare a surgery-only cohort with a radiotherapy cohort. The PRISMA guidelines were followed. Combined relative risk was calculated using DerSimonian-Laird random-effects model and a forest plot was drawn. RESULTS: We collected 183 manuscripts on early-stage cervical cancer treated with radical hysterectomy alone or with adjuvant radiotherapy after surgery. A total of eight studies met the inclusion criteria. Regarding oncological outcomes, survival was reported in five studies. The relative risk of recurrence and the relative risk of mortality was similar in both groups independently whether receive or not adjuvant therapy. Most of the studies did not report significant differences regarding morbidity treatment related between the groups, except for a higher rate of lymphedema after radiotherapy. CONCLUSION: We found that the relative risk of recurrence and mortality was similar in both groups not depending on adjuvant therapy. Therefore, whether radiotherapy adjuvant treatment is indicated remains a topic of debate.

BRCA1 mutations in high-grade serous ovarian cancer are associated with proteomic changes in DNA repair, splicing, transcription regulation and signaling.

Despite recent advances in the management of BRCA1 mutated high-grade serous ovarian cancer (HGSC), the physiology of these tumors remains poorly understood. Here we provide a comprehensive molecular understanding of the signaling processes that drive HGSC pathogenesis with the addition of valuable ubiquitination profiling, and their dependency on BRCA1 mutation-state directly in patient-derived tissues. Using a multilayered proteomic approach, we show the tight coordination between the ubiquitination and phosphorylation regulatory layers and their role in key cellular processes related to BRCA1-dependent HGSC pathogenesis. In addition, we identify key bridging proteins, kinase activity, and post-translational modifications responsible for molding distinct cancer phenotypes, thus providing new opportunities for therapeutic intervention, and ultimately advance towards a more personalized patient care.

Can We Reduce Overtreatment of Cervical High-Grade Squamous Intraepithelial Lesions?

OBJECTIVE: The aim was to evaluate the cytology, colposcopic, and pathological factors associated with the absence of high-grade squamous intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia (CIN) 2-3 lesion on loop electrosurgical excision procedure (LEEP) specimens in women with high-grade cytology and/or HSIL/CIN 2-3 biopsy and the risk of disease persistence/recurrence. MATERIALS AND METHODS: Two-center retrospective study of women undergoing LEEP for high-grade cervical disease between January 2014 and December 2019. Clinical, cytology, colposcopy, and pathology results were evaluated to identify independent predictive factors associated with CIN 1/negative LEEP results. Univariate and multivariate logistic regression models were performed. Follow-up data was evaluated to assess the risk of HSIL/CIN 2-3 persistence/recurrence. RESULTS: Six hundred thirty-nine of 801 women (79.8%) had high-grade cytology and 631 (78.8%) HSIL/CIN 2-3 biopsy. High-risk human papillomavirus test was positive in 98% of women. Loop electrosurgical excision procedure specimen showing CIN 1 or less was found in 27%-31%. Normal/low-grade colposcopy (odds ratio [OR] = 2.17, CI = 1.39-3.39, p = .001) and CIN 1/negative biopsy (OR = 3.25, CI = 2.12-4.99, p < .001) were predictors of negative/CIN 1 LEEP result in women with high-grade cytology. Normal/low-grade cytology (OR = 1.77, CI = 1.19-2.64, p = .005), normal/low-grade colposcopy (OR = 1.66, CI = 1.11-2.49, p = .013), and CIN 2 biopsy (OR = 2.75, CI = 1.73-4.39, p < .001) were predictors in women with HSIL/CIN 2-3 biopsy. Women with a negative/CIN 1 LEEP had lower recurrence/persistence than those with confirmed HSIL/CIN 2-3(1 vs 31, p = .002). Positive endocervical margin (OR = 2.85, CI = 1.10-7.36, p = .03) and high-risk human papillomavirus persistence (OR = 41.3, CI = 16-106.7, p < .01) were predictors of HSIL/CIN 2-3 persistence/recurrence. CONCLUSIONS: A CIN 1/negative LEEP specimen in women with high-grade cytology and/or HSIL/CIN 2-3 biopsy is associated with negative/low-grade cytology, normal/low-grade colposcopic findings and CIN 2 biopsy result before treatment. The HSIL/CIN 2-3 disease persistence/recurrence is low when LEEP specimen does not confirm HSIL/CIN 2-3.

Retro cervical tunneling to ensure correct placement for robotic-assisted transabdominal cerclage.

OBJECTIVE: To demonstrate the step-by-step surgical technique of robotic-assisted transabdominal cerclage, highlighting a new posterior compartment approach. DESIGN: Stepwise explanation of a surgical technique using surgical video. SETTING: The procedure was performed at the Obstetrics and Gynecology Department, Hospital Vall d'Hebron in Barcelona, Spain, a tertiary medical center. The local institutional review board considers that case reports are exempt from research approval. PATIENT(S): A 26-year-old non-pregnant patient, with a history of cervical incompetence, three second-trimester losses, and vaginal cerclage failure during her previous pregnancy. INTERVENTION(S): Robotic-assisted transabdominal cerclage placement was performed. An 8-mm, 30° scope; monopolar scissors; and Maryland bipolar graspers were used. A uterine manipulator was used for better exposure. First, a bladder flap was created, and the uterine vessels were identified and skeletonized. Next, a window between the uterine vessels and the uterine cervix at the level of the cervical-isthmic junction was created bilaterally. At the posterior compartment, the dissection of the root of the uterosacral ligaments was carefully performed. A retrocervical pocket was created with monopolar scissors and sharp dissection. The procedure was finished with the Mersilene tape placement. First, the tape was passed through the window created in the right broad ligament, with a posterior-to-anterior direction, the retro cervical pocket, and finally through the left broad ligament. The knot was placed anteriorly and reperitonization was performed. In addition to this operation, robotic-assisted transabdominal cerclage was successfully performed in another six patients with good surgical and obstetrics outcomes. MAIN OUTCOME MEASURE(S): Intraoperative technique to ensure successful robot-assisted abdominal cerclage placement. RESULT(S): The patient became pregnant six months following the robotic-assisted transabdominal cerclage. Her pregnancy was closely followed up at the High-Risk Obstetric Unit, and she had no complications during pregnancy. An elective cesarean section was performed at 36 weeks with a healthy newborn baby that was discharged with the mother three days after delivery. CONCLUSION(S): The development of a retro cervical pocket during robotic-assisted transabdominal cerclage can be performed safely and effectively. It may help prevent displacement of the Mersilene tape during endoscopic knotting.

Importance of Enhanced Recovery After Surgery (ERAS) Protocol Compliance for Length of Stay in Ovarian Cancer Surgery.

OBJECTIVES: Enhanced Recovery After Surgery (ERAS) programs include multiple perioperative care elements, which when implemented together are designed to improve recovery after surgery with subsequent reduction in hospital length of stay (LOS). The aim of this study is to examine the impact of ERAS protocol compliance on LOS in patients undergoing advanced ovarian cancer surgery within the context of a randomized clinical trial. METHODS: Patients were enrolled in a prospective, consecutive, interventional randomized clinical trial between June 2014 and March 2018. Women with either suspected or confirmed advanced ovarian cancer with International Federation of Gynecology and Obstetrics (FIGO) stages IIB-IVA and recurrent ovarian cancer, who underwent cytoreduction surgery, were randomly assigned to either a conventional management (CM) protocol or an ERAS protocol. Demographic items, preoperative clinical data, and surgical characteristics of patients were recorded, as were LOS and ERAS protocol compliance. Negative binomial regression was used to model the relation between length of stay and ERAS protocol compliance. RESULTS: We included 49 patients in the CM group and 50 patients in the ERAS group. The overall rate of ERAS compliance was 92%. We observed that increasing ERAS protocol compliance was associated with shorter median LOS, and in patients who underwent higher complex surgeries, the length of stay reduction was greater. CONCLUSION: This study identifies a correlation between increasing ERAS protocol compliance and decreasing LOS in ovarian cancer surgery. This finding underlines the necessity to implement as many ERAS protocol elements as possible to achieve optimal clinical outcome improvements.

Robot-assisted Extraperitoneal Para-aortic Lymphadenectomy Is Associated with Fewer Surgical Complications: A Post Hoc Analysis of the STELLA-2 Randomized Trial.

STUDY OBJECTIVE: To evaluate if extraperitoneal para-aortic lymphadenectomy (PALND) using a robot-assisted approach was associated with fewer complications than all other approaches (conventional laparoscopic transperitoneal or extraperitoneal and robot-assisted transperitoneal) without compromising lymph node yield, operative time, or length of stay. DESIGN: Post hoc analysis of the prospective randomized open-label multicenter trial (STELLA-2). SETTING: Three academic referral hospitals. PATIENTS: Two hundred and three eligible patients from the STELLA-2 trial were included. INTERVENTIONS: The patients were randomized to extraperitoneal or transperitoneal PALND using a minimally invasive approach (either laparoscopic or robot-assisted) for surgical staging of endometrial or ovarian cancer. The minimally invasive approaches were not subjected to randomization. MEASUREMENTS AND MAIN RESULTS: The primary end point was evaluated through a composite variable that included at least 1 of the following events: blood loss ≥500 mL during PALND, any intraoperative complication related to PALND, severe postoperative complication (Clavien-Dindo ≥grade IIIA), impossibility of completing the procedure, or conversion to laparotomy. Of the 203 patients analyzed, 68 were assigned to the extraperitoneal laparoscopic group (X-L), 62 to the transperitoneal laparoscopic group (T-L), 35 to the extraperitoneal robotic group (X-R), and 38 to the transperitoneal robotic group (T-R). A reduced trend in complications was observed in the extraperitoneal robot-assisted arm when considering the primary end point (X-L: 25.0%, T-L: 24.2%, X-R: 5.7%, T-R: 28.9%; p = .073). In a multivariable analysis, age (odds ratio [OR] 1.05; 95% confidence interval [CI], 1.00-1.09), body mass index (OR 1.09; 95% CI, 1.03-1.16), and waist-to-hip ratio (OR 1.66; 95% CI, 1.12-2.47) were found to independently increase the risk of PALND complications, whereas the extraperitoneal robotic approach (OR 0.13; 95% CI, 0.02-0.64) was an independent protective factor for complication occurrence. CONCLUSION: Robot-assisted extraperitoneal PALND is associated with fewer surgical complications, without compromising lymph node retrieval, operative time, or length of stay. Robot-enhanced 3D visualization, surgeon ergonomics, or hemostatic precision could explain our results.

Proteomic Studies on the Management of High-Grade Serous Ovarian Cancer Patients: A Mini-Review.

High-grade serous ovarian cancer (HGSC) remains the most common and deadly subtype of ovarian cancer. It is characterized by its late diagnosis and frequent relapse despite standardized treatment with cytoreductive surgery and platinum-based chemotherapy. The past decade has seen significant advances in the clinical management and molecular understanding of HGSC following the publication of the Cancer Genome Atlas (TCGA) researchers and the introduction of targeted therapies with anti-angiogenic drugs and poly(ADP-ribose) polymerase inhibitors in specific subgroups of patients. We provide a comprehensive review of HGSC, focusing on the most important molecular advances aimed at providing a better understanding of the disease and its response to treatment. We emphasize the role that proteomic technologies are now playing in these two aspects of the disease, through the identification of proteins and their post-translational modifications in ovarian cancer tumors. Finally, we highlight how the integration of proteomics with genomics, exemplified by the work performed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), can guide the development of new biomarkers and therapeutic targets.

Clinical Challenges in Managing Cervical Intraepithelial Neoplasia 2: A Report From a Cross-sectional Survey.

OBJECTIVES: The aims of the study were to determine the management strategies offered to women with cervical intraepithelial neoplasia 2 (CIN 2) and the attitude of colposcopists toward its histological diagnosis and to identify the criteria used to select women for conservative management. METHODS: Colposcopists working in Spain were invited to participate in an online questionnaire via the Spanish Gynecology and Colposcopy Societies. The survey included 42 questions covering the 3 objectives of the study. One hundred eighty-two colposcopists representing all autonomous regions in Spain responded. The response rate was 26.2%, considering the total number of members. RESULTS: Most colposcopists offer conservative management in selected cases (153/182). The preferred follow-up interval is 6 months (65%), followed by 3-4 months (30%). Observation was considered no longer appropriate after 24 months (29.5%) and 12 months (26.3%), and 24.3% expressed that it depended on women's plan to conceive. During conservative management, 93.9% always perform a cytology, 62.7% human papillomavirus testing, 96.8% colposcopy, 47.9% cervical biopsy, and 28.1% endocervical curettage. Forty-five percent consider that CIN 2 merely represents a misclassified CIN 1 or CIN 3, whereas 46.2% think that CIN 2 lesions are unlikely to regress. Most respondents considered that age older than 40 years (81.3%), human papillomavirus 16 infection (62.1%), HIV infection (76.8%), positive p16 immunostaining (60.2%), a large lesion occupying more than 50% of the cervix (87%), endocervical involvement (91.6%), and previous treatment for CIN 2-3 (77%) are contraindications for conservative management. CONCLUSIONS: Management of CIN 2 remains challenging for colposcopists, and a lack of consensus still exists in clinical practice. A better understanding of the natural history of CIN 2 and its clinical outcomes is still necessary to guide clinicians in its management.

Intraoperative Human Papillomavirus Test Predicts 24-Month High-Grade Squamous Intraepithelial Lesion Recurrence Saving Costs: A Prospective Cohort Study.

OBJECTIVES: The human papilloma virus (HPV) test is recommended in the posttreatment follow-up of cervical intraepithelial neoplasia. The aim of the study was to assess whether the intraoperative HPV (IOP-HPV) test had a similar diagnostic accuracy that HPV test performed at 6 months to predict high-grade squamous intraepithelial lesion (HSIL) recurrence. MATERIALS AND METHODS: In a prospective cohort study, 304 women diagnosed with HSIL by biopsy and/or endocervical curettage before treatment and/or confirmation in the histological specimen were included. Immediately after surgery, HPV testing was performed. This test was compared with the test at 6 months and other predictors of recurrence. Patients were followed for 24 months. An economic analysis was performed to compare the costs of IOP-HPV and HPV test at 6 months. RESULTS: Recurrence rate of HSIL was 6.2% (19 patients). The diagnostic accuracy of the IOP-HPV test to predict HSIL recurrence at 24 months was similar to the HPV test at 6 months, with comparative sensitivities of 100% versus 86.7%, specificities of 82.0% versus 77.9%, positive predictive values of 27.1% versus 18.1%, and negative predictive values of 100% versus 99.0%. Direct economic saving per high-grade intraepithelial lesion patient was 172.8 &OV0556;. CONCLUSIONS: The HPV test performed after loop electrosurgical resection procedure predicted recurrence of HSIL at 24 months with a similar diagnostic accuracy than the HPV test at 6 months. The use of the IOP-HPV test in the management of HSIL will allow early detection of the risk of recurrent disease and to save costs because of potential suppression of the need of HPV and follow-up controls at 6 months.

Nerve-sparing versus non-nerve-sparing radical hysterectomy: surgical and long-term oncological outcomes.

OBJECTIVES: There are controversies regarding the long-term oncological safety of preservation of pelvic innervation during radical hysterectomy (RH). This study aimed to analyze the feasibility and safety of nerve-sparing radical hysterectomy (NSRH) for cervical cancer compared with non-NSRH following 17 years of experience in a tertiary cancer referral center. MATERIALS AND METHODS: Between May 1999 and June 2016, all patients who underwent RH for cervical cancer were followed-up prospectively. Comparison analyses regarding surgical outcomes, complications, overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were performed between patients treated with NSRH and non-NSRH. RESULTS: A total of 188 patients were included (113 non-NSRH and 75 NSRH). The median follow-up was 112 months. Estimated blood loss and hospital stay were all significantly lower in the NSRH group. Overall intraoperative complication rate (p = 0.02) and need for transfusion (p = 0.016) were lower in the NSRH group. There were no differences in the median operation time, OS, DFS, CSS, or recurrence rates between the NSRH and non-NSRH group. CONCLUSIONS: Our study provides a wide perspective on the developments of nerve-sparing procedures for the management of women with early-stage cervical cancer. Our results suggest that NSRH is a feasible and safe procedure, with reduced morbidity outcomes.

Impact of surgical site infection (SSI) following gynaecological cancer surgery in the UK: a trainee-led multicentre audit and service evaluation.

OBJECTIVES: Surgical site infection (SSI) complicates 5% of all surgical procedures in the UK and is a major cause of postoperative morbidity and a substantial drain on healthcare resources. Little is known about the incidence of SSI and its consequences in women undergoing surgery for gynaecological cancer. Our aim was to perform the first national audit of SSI following gynaecological cancer surgery through the establishment of a UK-wide trainee-led research network. DESIGN AND SETTING: In a prospective audit, we collected data from all women undergoing laparotomy for suspected gynaecological cancer at 12 specialist oncology centres in the UK during an 8-week period in 2015. Clinicopathological data were collected, and wound complications and their sequelae were recorded during the 30 days following surgery. RESULTS: In total, 339 women underwent laparotomy for suspected gynaecological cancer during the study period. A clinical diagnosis of SSI was made in 54 (16%) women. 33% (18/54) of women with SSI had prolonged hospital stays, and 11/37 (29%) had their adjuvant treatment delayed or cancelled. Multivariate analysis found body mass index (BMI) was the strongest risk factor for SSI (OR 1.08[95% CI 1.03 to 1.14] per 1 kg/m2 increase in BMI [p=0.001]). Wound drains (OR 2.92[95% CI 1.41 to 6.04], p=0.004) and staple closure (OR 3.13[95% CI 1.50 to 6.56], p=0.002) were also associated with increased risk of SSI. CONCLUSIONS: SSI is common in women undergoing surgery for gynaecological cancer leading to delays in discharge and adjuvant treatment. Resultant delays in adjuvant treatment may impact cancer-specific survival rates. Modifiable factors, such as choice of wound closure material, offer opportunities for reducing SSI and reducing morbidity in these women. There is a clear need for new trials in SSI prevention in this patient group; our trainee-led initiative provides a platform for their successful completion.

Vaginal Intraepithelial Neoplasia: Clinical Presentation, Management, and Outcomes in Relation to HIV Infection Status.

OBJECTIVES: The data available on vaginal intraepithelial neoplasia (VAIN) and infection by HIV are scarce. We therefore aimed to review the clinical presentation, management, and survival outcomes of VAIN in this group of women. MATERIALS AND METHODS: This is an observational cohort study of women diagnosed with VAIN for a 23-year period. Clinical characteristics and outcomes were analyzed according to women's HIV infection status. Disease-free and progression-free survival were compared between groups. RESULTS: Twenty-two of 87 women were HIV positive (25.3%) compared with the HIV-negative group, HIV-positive women were younger (median age = 39 vs 57 years, p < .001) and more frequently smokers (p < .001). They also presented with multifocal and multicentric disease more often (p = .004 and p = .033, respectively) in relation to infection by human papillomavirus. All HIV-positive women were receiving antiretroviral treatment. The median time from the diagnosis of HIV to the development of VAIN was 14 years (range = 1-22 years). There were no significant differences in survival outcomes between groups. CONCLUSIONS: HIV-positive women are at an increased risk of developing VAIN and frequently present at a younger age with multifocal and multicentric disease. Vaginal intraepithelial neoplasia lesions can develop many years after the initial diagnosis of HIV infection reason why prolonged surveillance is essential to enable prompt diagnosis and treatment.