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Simple Summary: Magnetic resonance imaging plays a key role in preoperative staging and the evaluation of treatment responses of patients affected by cervical cancer. This is due to the ability to identify the involvement of adjacent structures such as the vagina and parametrium as well as lymph nodes. In those patients eligible for neoadjuvant treatment, the assessment of treatment response could help to plan a proper strategy to improve survival outcomes while minimizing side effects. This study aims to compare the diagnostic accuracy of magnetic resonance imaging for cervical cancer staging in subjects who underwent neoadjuvant treatment plus surgery with those who underwent direct surgery. Secondary objectives include accuracy comparison between magnetic resonance imaging and physical examination for detecting parametrium and vaginal involvement, and the accuracy in the evaluation of lymph node status. Our results show that the overall accuracy rate of magnetic resonance imaging in preoperative staging of cervical cancer does not seem to be satisfactory, especially when it is applied to pretreated patients. Magnetic resonance imaging (MRI) has been proven to ensure high diagnostic accuracy in the identification of vaginal, parametrial, and lymph node involvement in patients affected by cervical cancer (CC), thus playing a crucial role in the preoperative staging of the disease. This study aims to compare the accuracy of MRI for the preoperative staging of patients with CC who underwent neoadjuvant treatment (NAT) or direct surgery. Retrospective data analysis of 126 patients with primary CC International Federation of Gynecology and Obstetrics stage IB3-IIB who underwent NAT before radical surgery (NAT group = 94) or received surgical treatment alone (control arm = 32) was prospectively performed. All enrolled patients were clinically assessed with both a pelvic examination and MRI before surgical treatment. Data from the clinical examination were compared with the histopathological findings to assess the accuracy of MRI for staging purposes after NAT or before direct surgery. MRI showed an overall accuracy of 46.1%, proving it to be not superior to pelvic and physical examination. The overall MRI accuracy for the evaluation of parametrial, vaginal, and lymph node status was 65.8%, 79.4%, and 79.4%, respectively. In the NAT group, the accuracy for the detection of parametrial, lymph node, and vaginal involvement was lower than the control group; however, the difference was not significant (p ≥ 0.05). The overall accuracy of MRI for the preoperative staging of CC after NAT is shown to be not unsatisfactory. The limits of MRI staging are especially evident when dealing with pre-treated patients. [ABSTRACT FROM AUTHOR]

To predict the overall pathologic response to neoadjuvant chemotherapy (NACT) of patients with locally advanced cervical cancer (LACC) creating a prediction model based on clinical-pathological factors and biomarkers (p53, Bcl1 and Bcl2) and to evaluate the prognostic outcomes of NACT. This is a retrospective study of 88 consecutive patients with LACC who underwent NACT followed by nerve sparing surgery with retroperitoneal lymphadenectomy at National Cancer Institute of Milan, between January 2000 and June 2013. Clinical pathologic data were retrieved from the institutional database. Biomarkers (p53, Bcl1 and Bcl2) were evaluated before and after NACT in the specimen. To investigate their role as predictors of response, we tried several statistical machine learning algorithms. Responders to NACT showed a 5-years survival between 100%(CR) and 85.7%(PR). Clinical factors were the most important predictor of response. Age, BMI and grade represented the most important predictors of response at random forest analysis. Tree-based boosting revealed that after adjusting for other prognostic factors, age, grade, BMI and tumor size were independent predictors of response to NACT, while p53 was moderately related to response to NACT. Area under the curve (crude estimate): 0.871. Whereas Bcl1 and Bcl2, were not predictors for response to NACT. The final logistic regression reported that grade was the only significant predictor of response to NACT. Combined model that included clinical pathologic variables plus p53 cannot predict response to NACT. Despite this, NACT remain a safe treatment in chemosensitive patients avoiding collateral sequelae related to chemo-radiotherapy. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether primary conization might overcome the risk of local dissemination in patients undergoing laparoscopic radical hysterectomy.Methods: Consecutive data of 262 patients with early stage cervical cancer were retrieved: 88 women had conization followed by radical hysterectomy. A propensity-matched comparison (1:1) was carried out in order to compare laparoscopy and open surgery. Accumulating data highlighted that minimally invasive surgery has been associated with higher recurrence rates and worse overall survival than open surgery in women with early stage cervical cancer.Results: Data of 35 paired patients (total 70 patients) were analyzed. No between-group differences in baseline, disease, and pathological variables were observed. Patients undergoing laparoscopy correlated with lower blood loss (50 [range 30-100] vs 150 [range 50-500] mL; P<0.001) and shorter length of stay (3 ± 0.8 vs 5.4 ± 1.4 days; P<0.001) compared to open surgery. One local recurrence was observed per group (P=1.00). Type of surgical approach did not influence site of recurrence (P=1.00) or survival outcomes, in terms of 10-year disease-free (P=0.549, log-rank test) and overall survivals (P=0.615, log-rank test).Conclusions: The data show that primary conization might overcome the risk of local recurrence after laparoscopic radical hysterectomy in early stage cervical cancer. Further prospective evidence is needed. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is causatively associated with cervical cancer (CC), the fourth most common malignant disease of women worldwide. The introduction of first generation prophylactic HPV vaccines in several national vaccination programmes has substantially decreased the global incidence of HPV cervical infections. Despite the success obtained, the two-licenced bivalent and quadrivalent L1 (the major HPV capsid protein) virus-like particle (VLP)-based vaccines (2vHPV and 4vHPV) present some limitations, such as a virus-type restricted protection, the high cost of the manufacture, and an absence of therapeutic activity on the established lesions. The second-generation prophylactic HPV vaccines, constituted by alternative viral components (such as capsomere or minor capsid HPV L2 protein) or made by more cost-effective strategies of production, are undergoing an intense clinical evaluation. This review aims to offer the reader a complete and updated overview on the HPV vaccination. The authors describe the effectiveness and the limitations of the approved HPV vaccines, and highlight the main characteristics of the new generation vaccines. IMPACT STATEMENT What is already known on this subject? CC is the fourth most common cancer of women in the world. HPV is the etiologic cause of almost all CCs. After being approved by the FDA, the first prophylactic 2vHPV and 4vHPV have been implemented into a routine vaccination schedule around the world, substantially decreasing the incidence of HPV and related-diseases in countries with high coverage rates. Currently, research is focusing on finding innovative and alternative systems to produce and deliver new HPV vaccines, overcoming all of the limitations that have partly restricted the potential benefit of previous vaccines on public health. What do the results of this study add? This narrative review was performed to find all the published studies reporting the efficacy and limitations of 2vHPV and 4vHPV, and evaluating the new HPV vaccines under pre- and clinical investigation. What are the implications of these findings for clinical practice and/or further research? Next generation of HPV vaccines will address many, if not all, of the limitations associated with current vaccines and will represent a step forward in the fight against CC. [ABSTRACT FROM AUTHOR]

Objective: To assess the risk of developing high-grade cervical dysplasia among women with low-grade cervical cytology and nonvisible squamocolumnar junction (SCJ) at colposcopic examination. Methods: Data of consecutive women with low-grade intraepithelial lesion(≤LSIL) undergoing colposcopic examination, which was unsatisfactory (due to the lack of the visualization of the entire SCJ), were retrospectively reviewed. The risk of developing high-grade cervical intraepithelial neoplasia (CIN2+) was assessed using Kaplan-Meier and Cox models. Results: Data of 86 women were retrieved. Mean (standard deviation [SD]) age was 36.3 (13.4) years. A total of 71 (82.5%) patients had high-risk human papillomavirus (HR-HPV) at the time of diagnosis. Among the 63 patients undergoing repetition of HPV testing, 15 (24%) and 48 (76%) women had positive and negative tests for HR-HPV at 12 months, respectively. We observed that 5 (33%) of 15 patients with HPV persistence developed CIN2+, while only 1 (2%) patient of 48 patients without HPV persistence developed CIN2+ (odds ratio [OR]: 23.5; 95% confidence interval [CI]: 2.46-223.7; P < .001). The length of HR-HPV persistence correlated with an increased risk of developing CIN2+ (P < .001; P for trend). High-risk HPV persistence is the only factor predicting for CIN2+ (hazard ratio: 3.19; 95% CI: 1.55-6.57; P = .002). Conclusions: High-risk HPV persistence predicts the risk of developing CIN2+ in patients with unsatisfactory colposcopic examination. Further studies are warranted in order to implement the use of HPV testing in patients with unsatisfactory colposcopy. [ABSTRACT FROM AUTHOR]

Background: Chemoradiotherapy (CRT) is the standard of care for locally advanced cervical cancer (LACC). Pre-treatment lymph nodes (LN) assessment may have an important therapeutic role. CRT followed by adjuvant chemotherapy increased progression free survival (PFS) and overall survival (OS). Our study evaluated the feasibility and the effectiveness of a trimodality strategy in patients with LACC and positive LN. Methods: Consecutive patients with LACC treated at the National Cancer Institute of Milan were enrolled. All patients underwent pelvic and para-aortic extraperitoneal laparoscopic lymphadenectomy to assess the nodal status. After surgery, patients received radiotherapy followed by chemotherapy according to the stage of disease. Results: Between April 2012 and October 2013, 19 cervical cancer patients were enrolled. Overall, 10 (52.6%) patients presented with positive LN: 6 in the pelvic area and 4 both in the pelvic and para-aortic area. No perioperative major complications occurred. The most common surgical-related adverse events were bleeding (26%), respiratory distress (5%), infection (5%) and the development of lymphoceles (25%). Overall, 15 (78.9%) complete responses and 2 (10.5%) partial responses were registered. After a median follow-up of 43.3 months, 89.5% of patients were alive at the last visit, and 3-year PFS was 63%. Conclusions: Trimodality treatment appears feasible, well tolerated and promising in terms of oncologic outcome. [ABSTRACT FROM AUTHOR]

Objective: Nerve-sparing radical hysterectomy (NSRH) was introduced with the aim to reduce pelvic dysfunctions related to conventional radical hysterectomy (RH). Here, we sought to assess the effectiveness and safety of NSRH in a relatively large number of the patients of cervical cancer (CC) patients undergoing either primary surgery or neoadjuvant chemotherapy (NACT) followed by surgery. Methods: Outcomes of consecutive patients undergoing NSRH and of a historical cohort of patients undergoing conventional RH were retrospectively reviewed. Results: This study included 325 (49.8%) and 327 (50.2%) undergoing NSRH and RH, respectively. Via a multivariable model, nodal status was the only factor predicting for DFS (hazard ratio [HR]=2.09; 95% confidence interval [CI]=1.17-3.73; p=0.01). A trend towards high risk of recurrence was observed for patients affected by locally advanced cervical cancer (LACC) undergoing NACT followed by surgery (HR=2.57; 95% CI=0.95-6.96; p=0.06). Type of surgical procedures (NSRH vs. RH) did not influence risk of recurrence (p=0.47). Similarly, we observed that the execution of NSRH rather than RH had not a detrimental effect on OS (HR=1.19; 95% CI=0.16-9.01; p=0.87). Via multivariable model, no factor directly correlated with OS. No difference in early complication rates was observed between the study groups. Conversely, a significant higher number of late complications was reported in RH versus NSRH groups (p=0.02). Conclusion: Our data suggested that NSRH upholds effectiveness of conventional RH, without increasing recurrence and complication rates but improving pelvic dysfunction rates. [ABSTRACT FROM AUTHOR]

Few studies have investigated the efficacy and safety of the nerve-sparing approach via minimally invasive surgery for the treatment of cervical cancer. We aimed to review the current evidence comparing nerve-sparing minimally invasive radical hysterectomy (NS-MRH) with conventional minimally invasive radical hysterectomy (MRH). This systematic review was registered in the International Prospective Register of Systematic Reviews (CRD#57655). Overall, 675 patients were included: 350 (51.9%) and 325 (48.1%) patients undergoing MRH and NS-MRH, respectively. MRH was associated with a shorter operative time in comparison with NS-MRH (mean difference = 32.57 minutes; 95% CI, 22.87-42.48). The estimated blood loss (mean difference = 97.14 mL, 20.01-214.29) and transfusion rate (odds ratio [OR] = 0.67; 95% confidence interval [CI], 0.15-3.01) did not differ statistically between the 2 groups. The risk of developing intraoperative (OR = 0.43; 95% CI, 0.08-2.23) and severe postoperative (OR = 0.63; 95% CI, 0.17-2.39) complications was similar between NS-MRH and MRH. Patients undergoing NS-MRH experienced lower voiding (OR = 0.39; 95% CI, 0.19-0.81) dysfunction rates than patients undergoing MRH. Moreover, a trend toward lower sexual (OR = 0.25; 95% CI, 0.06-1.07) and rectal (OR = 0.12; 95% CI, 0.01-1.02) issues was observed for patients having NS-MRH compared with patients undergoing MRH. Survival outcomes are not influenced by the type of surgical approach (recurrence [OR = 1.27; 95% CI, 0.49-3.28] and death [OR = 1.01; 95% CI, 0.36-2.83]) rates. The pooled data suggested that NS-MRH is equivalent to MRH for the treatment of cervical cancer and may be superior in reducing pelvic floor dysfunction rates. However, because of the low level of evidence of the included studies, further randomized trials are warranted. [ABSTRACT FROM AUTHOR]

Objective: Transfusions represent one of the main progresses of modern medicine. However, accumulating evidence supports that transfusions correlate with worse survival outcomes in patients affected by solid cancers. In the present study, we aimed to investigate the effects of perioperative blood transfusion in locally advanced cervical cancer. Methods: Data of consecutive patients affected by locally advanced cervical cancer scheduled to undergo neoadjuvant chemotherapy plus radical surgery were retrospectively searched to test the impact of perioperative transfusions on survival outcomes. Five-year survival outcomes were evaluated using Kaplan-Meier and Cox models. Results: The study included 275 patients. Overall, 170 (62%) patients had blood transfusion. Via univariate analysis,we observed that transfusion correlated with an increased risk of developing recurrence (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.09-4.40; P = 0.02). Other factors associated with 5-year disease-free survival were noncomplete clinical response after neoadjuvant chemotherapy (HR, 2.99; 95%CI, 0.92-9.63;P= 0.06) and pathological (P= 0.03) response at neoadjuvant chemotherapy as well as parametrial (P= 0.004), vaginal (P G 0.001), and lymph node (P = 0.002) involvements. However, via multivariate analysis, only vaginal (HR, 3.07; 95%CI, 1.20-7.85; P = 0.01) and lymph node involvements (HR, 2.4; 95% CI, 1.00-6.06; P = 0.05) correlate with worse disease-free survival. No association with worse outcomes was observed for patients undergoing blood transfusion (HR, 2.71; 95% CI, 0.91-8.03; P = 0.07). Looking at factors influencing overall survival, we observed that lymph node status (P = 0.01) and vaginal involvement (P = 0.06) were independently associated with survival. Conclusions: The role of blood transfusions in increasing the risk of developing recurrence in LAAC patients treated by neoadjuvant chemotherapy plus radical surgery remains unclear; further prospective studies are warranted. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To analyze local recurrence rate (LRR), morbidities and oncologic outcome of class III nerve-sparing radical hysterectomy. Patients and methods: 170 consecutive class III NSRH cases were performed. Nineteen patients were addressed directly to surgery whilst neoadjuvant chemotherapy was administered in 151 patients. The majority of patients had SCC (75%). The median follow-up was 31months. Results: The mean age was 50 [27–78] years. Mean post-operative hospital stay was 7 [3–16] days. 2 intraoperative complications occurred. Operating time and blood loss was similar to the state-of-the-art of conventional radical hysterectomy. Overall G3-4 complication rate was 8.2 % (14/170). Early G3-4 complication rate was 3.5% (6/170). Late G3-4 complication rate was: 4.7%. (8/170). Positive pelvic nodes were noted in 31 patients (18.2%). Vagina and parametrial involvement were present in 38 (22%) and 27 (15.8%) patients, respectively. LRR was 10% (17/170). The sites of relapse were: 12 pelvic, 5 vaginal. There were 9 patients DOD. The 2-year and 5-year DFS rates were 89% and 81%, respectively. Univariate and multivariate analysis identified vagina involvement and postoperative treatment as significant prognostic factors. Conclusions: The oncologic results of NSRH were similar to the state-of-the-art of conventional radical hysterectomy. Two years DFS in relation to FIGO stage of disease was 92.3, 89.2 and 86.1 % respectively for IB1, IB2, IIB comparable to literature data. The early and late complications rate related to autonomic injury was significantly lower. The nerve-sparing technique should be considered in all cervical cancer patients addressed to surgery. [ABSTRACT FROM AUTHOR]

To demonstrate the efficacy and feasibility of preoperative chemoradiation followed by radical surgery in a consecutive series of patients with stage IIIB cervical cancer.Between October 1997 and July 2007, 39 patients with International Federation of Gynecology and Obstetrics stage IIIB cervical cancer were consecutively staged and treated at the Catholic University of Rome and Campobasso and at the National Cancer Institute of Milan. Radical surgery was performed 5 to 6 weeks after the end of the cisplatinum-based neoadjuvant chemoradiation.Clinical responses were observed in 35 patients (92.1%): 6 (15.8%) complete and 29 (76.3.8%) partial. Radical surgery was performed in 35 patients (89.7%). According to Chassagne classification, we observed 7 (20.0%) grade 3, 17 (48.6%) grade 2, and 28 (80%) grade 1 surgical complications. At pathological examination, 12 patients (34.3%) showed complete response, 7 patients (20.0%) had only a microscopic disease, 8 patients (22.8%) had a partial response, and the last 8 patients (22.8%) had no change in disease. We registered 11 (31.4%) operative and 4 (11.4%) early postoperative complications. Median follow-up was 33 months (range, 3-80 months). The percentages of 3-year disease-free survival and overall survival were 67.6% and 70.0%, respectively. Patients with complete response and microscopic disease showed better prognosis than patients with partial response and no change (3-year disease-free survival, 100% vs 31%; and 3-year overall survival, 100% vs 39%).Chemoradiation followed by radical hysterectomy could be administered in patients with stage IIIB cervical cancer with an acceptable rate of complications and with a survival outcome similar to that of chemoradiotherapy, allowing the assessment of pathological response with its implication on clinical outcomes. [ABSTRACT FROM AUTHOR]

To compare quality of life and bladder, intestinal, and sexual dysfunctions in 2 groups of patients undergoing different types of radical hysterectomies (RHs).Patients with cervical cancer who underwent RH have been enrolled in a questionnaire-based study. Quality of life (QoL) and bladder, intestinal, and sexual dysfunctions were evaluated with the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx). Patients were grouped according to the type of RH: group 1, class II RH and group 2, class III nerve-sparing RH (NSRH).Of 157 women included in the study, 127 filled out the questionnaire. Overall, QoL score assessed with the FACT questionnaire did not differ significantly between the 2 groups. The FACT subscales assessing physical, functional, emotional, and social well-being did not differ significantly between the 2 groups, whereas the FACT-Cx subscales assessing disease-related symptoms in group 2 patients showed a significantly worse score (72 vs 66; P = 0.03). Evaluating singularly the 15 items of the Cx subscales assessing disease-related symptoms, we did not find any significant difference between the 2 groups, but only Cx1 ("I am bothered by discharge or bleeding from my vagina") was significantly worse in group 2 patients. At univariate analysis, we found that NSRH and adjuvant radiotherapy (RT) impact negatively on the FACT-Cx subscales regarding pelvic visceral function. However, at multivariate analysis, only adjuvant RT impact negatively.Patients submitted to class III NSRH did not present worse QoL and pelvic visceral dysfunctions when compared with class II RH. The RT seems to be a factor impacting negatively on bladder and sexual function. [ABSTRACT FROM AUTHOR]

Then, minimally invasive nerve-sparing radical hysterectomy improves both peri-operative outcomes and pelvic floor dysfunctions, thus representing a win-win scenario for cervical cancer patients [[8]]. Although minimally invasive nerve sparing radical hysterectomy is associated with improved preoperative outcomes in comparison with open surgery, the potential detrimental oncologic results related to the execution of a minimally invasive procedure limited the adoption of laparoscopic and robotic assisted procedures in this setting. [Extracted from the article]

Abstract: Objectives : According to our previous experience, Type III Nerve-sparing Radical hysterectomy (NSRH) for cervical cancer presented an acceptable urologic morbidity, without compromising radicality. The aim of this study was to compare Type NSRH with other types of RH in terms of incidence of early bladder dysfunctions and perioperative complications. Methods : One hundred and ten patients with cervical cancer were submitted to Type II RH (group 1), Type III NSRH (group 2) and Type III RH (group 3). We assessed the postoperative early bladder function and complications. The follow-up period was 3 months. Results : Group 1 had a significantly shorter duration of the surgery, minor mean blood loss and shorter mean length of postoperative stay when compared to groups 2 and 3. No intraoperative complications were reported in either of the groups. The groups did not differ significantly in terms of GIII/IV morbidity (group 1 = 10%, group 2 = 10% and group 3 = 15%, χ 2, P value: 0.65). Not even they differed in terms of urologic GI–IV morbidity (group 1 = 13%, group 2 = 15% and group 3 = 10%, χ 2, P value = 0.88). Groups 1 and 2 presented a prompt recover of bladder function, significantly different from that of group 3. There was a significant difference between the groups regarding the number of patients discharged with self-catheterism (group 1 = 0; group 2 and group 3 = 11; χ 2, P value ≪ 0.05). Conclusions : The Type III NSRH seems to be comparable to Type II RH and superior to Type III RH in terms of early bladder dysfunctions. [Copyright &y& Elsevier]

Accumulating evidence suggested the detrimental effects of adopting minimally invasive surgery in the management of early-stage cervical cancer. However, long-term evidence on the role of minimally invasive radical hysterectomy in "low-risk" patients exists. This is multi-institutional retrospective study comparing minimally invasive and open radical hysterectomy in low-risk early-stage cervical cancer patients. A propensity-score matching algorithm (1:2) was used to allocate patients into the study groups. Kaplan-Meir model was used to estimate 10-year progression-free and overall survival. Charts of 224 "low-risk" patients were retrieved. Overall, 50 patients undergoing radical hysterectomy were matched with 100 patients undergoing open radical hysterectomy. Minimally invasive radical hysterectomy was associated with a longer median operative time (224 (range, 100–310) vs. 184 (range, 150–240) minutes; p < 0.001), lower estimated blood loss (10 (10-100) vs. 200 (100−1000) ml, p < 0.001), and shorter length of hospital stay (3.8 (3-6) vs. 5.1 (4-12); p < 0.001). Surgical approach did not influence the risk of having intra-operative (4% vs. 1%; p = 0.257) and 90-day severe (grade 3+) postoperative complication rates (4% vs. 8%; p = 0.497). Ten-year disease-free survival was similar between groups (94% vs. 95%; p = 0.812; HR:1.195; 95%CI:0.275, 5.18). Ten-year overall survival was similar between groups (98% vs. 96%; p = 0.995; HR:0.994; 95%CI:0.182, 5.424). Our study appears to support emerging evidence suggesting that, for low-risk patients, laparoscopic radical hysterectomy does not result in worse 10-year outcomes compared to the open approach. However, further research is needed and open abdominal radical hysterectomy remains the standard treatment for cervical cancer patients. • 10-year overall survival in low-risk cervical cancer patients is higher than 95%. • Surgical approach does not influence survival outcomes in the low-risk population. • Minimally invasive radical hysterectomy does not reduce morbidity in the low-risk population. [ABSTRACT FROM AUTHOR]

Abstract: Objectives. : This paper reviews the evolution of concepts concerning the nerve-sparing radical hysterectomy (NSRH) in cervical cancer. Methods. : Research studies published between 1991 and 2006 were reviewed. Results. : Significant progress has been made in understanding the neuroanatomy and the neurophysiology of autonomic pelvic plexus. The ideal surgical management of cervical cancer patients should be tailored on the basis of prognostic factors and quality of life. Within the discussion concerning the optimal level of radicality of hysterectomy, which is still controversial, the new concept of NSRH has to be considered in order to reduce morbidity without compromising the oncological disease control. Surgical strategies have been developed to spare the autonomic functions with promising results. Conclusions. : To date, there is a growing body of data about NSRH in cervical cancer. However, there is not yet a consensus concerning to which part of uterine support ligaments a NS approach should be directed. [Copyright &y& Elsevier]

In high income setting, the massive implementation of screening programs has reduced the incidence of cervical cancer, dramatically. However, cervical cancer still remains a major health concern, being one of the most common cause of death for cancer among women. The adoption of primary prevention through vaccination against HPV aims to reduce the prevalence of HPV-related lesions and cervical cancer. Accumulating data highlighted the cost-effectiveness of introducing HPV vaccination for adolescent and young adults. In the present review, we critically evaluated the role of vaccination against HPV, focusing much more on the role of vaccination in specific cluster of subjects (eg, post-treatment and older adults). Additionally, we evaluated the available evidence on the role of vaccination in HIV-positive subjects and in women receiving solid organs transplantation. We observed that although vaccination might be considered effective in those cluster of subjects; further evidence is needed to assess the cost-effectiveness of vaccination in these settings. • The implementation of vaccination against HPV reduced the burden of cervical cancer. • Vaccination against HPV might have a role in patients undergoing conization. • Cost-effectiveness of HPV vaccination in HIV positive individuals deserves to be addressed. [ABSTRACT FROM AUTHOR]

In the recent years, minimally invasive surgery has emerged as the gold standard for the treatment of both benign and malignant gynecological conditions. Growing evidence suggest that laparoscopic and robotic-assisted treatments allow to archived the same long-term outcomes than conventional open abdominal treatments, minimizing peri-operative morbidity. In the present review we analyzed the advances in the treatment of cervical cancer patients, reporting the advances in both the evolution of concept of radical hysterectomy and of the adoption of minimally invasive surgery. We discussed the advantages related to the introduction of minimally invasive treatment for cervical cancer patients; innovation of conventional laparoscopic surgery as discussed as well. Recent evidence suggested a potential detrimental effect on long-term survival outcomes related to the use of minimally invasive surgery in patients affected by cervical cancer. However, reasons why minimally invasive surgery might have a detrimental effect are still unclear. Further evidence is needed in order to improve quality of treatment for cervical cancer patients. [ABSTRACT FROM AUTHOR]

To evaluate the long-term outcomes of young early stage cervical cancer patients wishing to preserve their childbearing potential. Data of young (aged <40 years) patients with early stage cervical cancer were prospectively collected. All patients with stage IA2, IB1 and IB2 cervical cancer were included; they have cervical conization and pelvic node dissection performed via minimally invasive surgery. Survival outcomes were assessed with the Kaplan-Meier model. Overall, 32 patients met the inclusion criteria. Mean (SD) age of the population included was 33 (±4). According to the FIGO 2018 staging system, the stage of disease was IA2, IB1 and IB2 in 9 (28%), 21 (66%) and 2 (6%) cases, respectively. All patients included had cervical conization and laparoscopic pelvic node assessment, including systematic pelvic lymphadenectomy (N = 30, 94%) and sentinel node mapping (N = 2, 6%). In six (19%) patients the planned conservative treatment was discontinued. Median follow-up was 75 (range, 12–184) months. No recurrent disease was diagnosed among patients undergoing conservative treatment; while 2 out of 6 patients having definitive surgical or radiotherapy treatments developed recurrent disease. Five-year disease free and overall survivals were 94% and 97%, respectively. Considering reproductive outcomes, 11 (69%) out of 16 patients who attempted to conceive got pregnant. Cervical conization and pelvic nodes assessment could be considered a valid treatment modality for early-stage cervical cancer patients who are wishing to preserve their childbearing potential. • Cervical conization plus lymph node dissection is a valuable option for early-stage stage cervical cancer. • About 20% for patients initially submitted to fertility sparing procedure required radical treatments. • In case of negative margins, cervical conization guarantees a good local disease control rate. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is the most common sexually transmitted disease, worldwide. Primary prevention thorough vaccination si able to reduce the burden of HPV-related lesions. Ten years ago the Food and drug Administration (FDA) approved the first vaccine against HPV. In the last decades, growing data on safety and effectiveness have been collected. In the present review we report the current knowledge on vaccine against HPV, highlighting the current value and prospective regarding the widespread diffusion of HPV vaccines. The role of emerging therapeutic vaccines is reviewed. [ABSTRACT FROM AUTHOR]

Objective: To investigate the impact of hematologic toxicity and leukopenia in locally advanced cervical cancer patients undergoing neoadjuvant chemotherapy (NACT).Study Design: Data of consecutive patients undergoing platinum-based NACT followed by surgery were retrospectively searched in order to evaluate the impact of chemotherapy-related toxicity on survival outcomes. Toxicity was graded per the Common Terminology Criteria for Adverse Events (CTCAEv.4.03). Survival outcomes were evaluated using Kaplan-Meir and Cox hazard models.Results: Overall, 126 patients were included. Among those, 94 (74.6%) patients experienced grade2+ hematologic toxicity; while, grade2+ non-hematologic toxicity occurred in 11 (8.7%) patients. After a median follow-up of 37.1 (inter-quartile range, 12-57.5) months, 21 (16.6%) patients experienced recurrence. Via multivariate analysis, no factor was independently associated with disease-free survival; while a trend toward worse prognosis was observed for patients experiencing grade2+ leukopenia at cycle-3 (HR:3.13 (95%CI: 0.94, 10.3); p=0.06). Similarly, grade2+ leukopenia (HR:9.98 (95%CI: 1.14, 86.6); p=0.03), lymph-node positivity (HR:14.6 (95%CI:1.0, 214.4); p=0.05) and vaginal involvement (HR:5.81 (95%CI:1.43, 23.6); p=0.01) impacted on overall survival, at multivariate analysis. Magnitude of leukopenia correlated with survival (p<0.001).Conclusions: Although, our data have to be confirmed by prospective investigations, the present study shows an association between the occurrence of leukopenia and survival outcomes. NACT-related immunosuppression might reduce the response against the tumor, thus promoting cancer progression. [ABSTRACT FROM AUTHOR]

To evaluate the impact of various HPV types on the risk of developing lesions of the uterus (either uterine cervix and endometrium) in women diagnosed with "atypical glandular cells" (AGC) at Pap smear. This is a multi-institutional retrospective study. Data of women diagnosed with AGC were retrospectively reviewed. All patients included had data about HPV DNA testing and 1-year clinical follow-up. Overall, chart of 480 patients were evaluated. After the exclusion of 286 patients, data of 194 patients were available for the analysis. Mean age was 43.9 (±6.0) years. HPV infection was documented in 136 women (70.1 %). Among HPV positive patients the risk of having/developing a lesion was 33.8 % (n = 46). Lesions included low- (L-SIL) and high- (H-SIL) squamous intraepithelial lesions, in situ adenocarcinoma of the uterine cervix, invasive cancer of the uterine cervix, endometrial hyperplasia and endometrial cancer in 16 (11.7 %), 18 (13.2 %), 6 (4.4 %), 3 (2.2 %), 2 (1.5 %) and 1 (1%), respectively. Among HPV negative patients the risk of having/developing a lesion was 15.5 %. They included l -SIL, H-SIL, in situ adenocarcinoma, endometrial hyperplasia and endometrial cancer in 1 (1.7 %), 1 (1.7 %), 1 (1.7 %), 3 (5.1 %) and 3 (5.1 %), respectively. Patients diagnosed with HPV16 were at higher risk of having/developing cervical lesions in comparison to patients with other HPV infections (p < 0.01). In comparison to other HPV types, the presence of HPV 18, 31, 33, and 45 did not increase the risk of developing a lesion over the time (p > 0.2). HPV positive patients were at higher risk of being diagnosed with a cervical lesion within 6 months from detection of AGC. Patients diagnosed with AGC are at risk to have / developing cervical and uterine lesions. Further prospective evidence is needed. [ABSTRACT FROM AUTHOR]