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Background: Cervical dysplasia persistence/recurrence has a great impact on women’s health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18–89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5–52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+.

The combination of primary and secondary prevention has already influenced the colposcopic practice by reduction in HPV (human papillomavirus) vaccine-type HSIL (HIGH-GRADE SIL), colposcopy referral numbers, colposcopic positive predictive value (PPV) for CIN2+, and by modification of referral pattern, colposcopic performance, and procedures. Different strategies, both isolated and combined, have been proposed in order to maintain the diagnostic accuracy of colposcopy: patient risk stratification based on immediate or future risk of CIN3+ or on HPV genotyping after a positive screening test. Data are needed to support alternative colposcopic strategies based on vaccination status and on the application of artificial intelligence where the patient’s risk stratification is implicit in precision medicine which involves the transition from an operator-dependent morphology-based to a less-operator dependent, more biomolecular management. The patient’s risk stratification based on any combination of “history” and “test results” to decrease colposcopy workload further reduce colposcopic and histologic morphological approaches, while adding genotyping to the risk stratification paradigm means less cytologic morphologic diagnosis. In Italy, there is a strong colposcopic tradition and there is currently no immediate need to reduce the number of colposcopies. Instead, there is a need for more accredited colposcopists to maintain the diagnostic accuracy of colposcopy in the vaccination era.

Background: Primary prevention through vaccination is a prophylactic approach aiming to reduce the risk of developing human papillomavirus (HPV)-related lesions. No mature and long-term data supported the adoption of vaccination in women undergoing conization. Methods: This is a retrospective multi-institutional study. Charts of consecutive patients undergoing conization between 2010 and 2014 were collected. All patients included had at least 5 years of follow-up. We compared outcomes of patients undergoing conization plus vaccination and conization alone. A propensity-score matching algorithm was applied in order to reduce allocation biases. The risk of developing recurrence was estimated using Kaplan-Meir and Cox hazard models. Results: Overall, charts of 1914 women were analyzed. The study group included 116 (6.1%) and 1798 (93.9%) women undergoing conization plus vaccination and conization alone, respectively. Five-year recurrence rate was 1.7% (n = 2) and 5.7% (n = 102) after conization plus vaccination and conization alone, respectively (p = 0.068). After the application of a propensity-score matching, we selected 100 patients undergoing conization plus vaccination and 200 patients undergoing conization alone. The crude number of recurrences was 2 (2%) and 11 (5.5%) for patients undergoing conization plus vaccination and conization alone, respectively (p = 0.231). Vaccination had no impact on persistent lesions (no negative examination between conization and new cervical dysplasia; p = 0.603), but reduced the risk of recurrent disease (patients who had at least one negative examination between conization and the diagnosis of recurrent cervical dysplasia; p = 0.031). Conclusions: Patients having vaccination experience a slightly lower risk of recurrence than women who had not, although not statistically significantly different. Further evidence is needed to assess the cost effectiveness of adopting vaccination in this setting.

Human papillomavirus (HPV) related cervical cancer represents an issue of public health priority. The World Health Organization recommended the introduction of HPV vaccination in all national public programs. In Europe, vaccines against HPV have been available since 2006. In Italy, vaccination is recommended and has been freely offered to all young girls aged 11 years since 2008. Three prophylactic HPV vaccines are available against high- and low-risk genotypes. The quadrivalent vaccine contains protein antigens for HPV 6, 11, 16, and 18. The bivalent vaccine includes antigens for HPV 16 and 18. The nonavalent vaccine was introduced in 2014, and it targets HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Clinical trials demonstrated the effectiveness of the three vaccines in healthy young women. Likewise, all vaccines showed an excellent safety profile. The bivalent vaccine provides two doses in subjects aged between 9 and 14 years and three doses in subjects over 14 years of age. The quadrivalent vaccine provides two doses in individuals from 9 to 13 years and three doses in individuals aged 14 years and over. The nonavalent vaccine schedule provides two doses in individuals from 9 to 14 years of age and three doses in individuals aged 15 years and over at the time of the first administration. Preliminary results suggest that the HPV vaccine is effective in the prevention of cervical squamous intraepithelial lesions even after local treatment. Given these outcomes, in general, it is imperative to expand the vaccinated target population. Some interventions to improve the HPV vaccine’s uptake include patient reminders, physicians-focused interventions, school-based vaccinations programs, and social marketing strategies. The Italian Society of Colposcopy and Cervico-Vaginal Pathology (SICPCV) is committed to supporting vaccination programs for children and adolescents with a catch-up program for young adults. The SICPCV also helps clinical and information initiatives in developing countries to decrease the incidence of cervico-vaginal and vulvar pathology.

The objective of this work is to assess the 5-year outcomes of patients undergoing conization for high-grade cervical lesions that simultaneously present as risk factors in the persistence of HPV infection and the positivity of surgical resection margins. This is a retrospective study evaluating patients undergoing conization for high-grade cervical lesions. All patients included had both positive surgical margins and experienced HPV persistence at 6 months. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). The charts of 2966 patients undergoing conization were reviewed. Among the whole population, 163 (5.5%) patients met the inclusion criteria, being at high risk due to the presence of positive surgical margins and experiencing HPV persistence. Of 163 patients included, 17 (10.4%) patients developed a CIN2+ recurrence during the 5-year follow-up. Via univariate analyses, diagnosis of CIN3 instead of CIN2 (HR: 4.88 (95%CI: 1.10, 12.41); p = 0.035) and positive endocervical instead of ectocervical margins (HR: 6.44 (95%CI: 2.80, 9.65); p < 0.001) were associated with increased risk of persistence/recurrence. Via multivariate analyses, only positive endocervical instead of ectocervical margins (HR: 4.56 (95%CI: 1.23, 7.95); p = 0.021) were associated with worse outcomes. In this high-risk group, positive endocervical margins is the main risk factor predicting 5-year recurrence.