Recurrent Cervical Intraepithelial Neoplasia Research Articles

Development of a nomogram for predicting postoperative recurrence of cervical intraepithelial neoplasia using immunohistochemical and clinical parameters

ABSTRACT Background We aimed to develop a nomogram to predict abnormal follow-up results of co-testing for cytology and human papillomavirus (HPV) in cervical intraepithelial neoplasia (CIN) patients after conization. Research design and methods Two hundred sixty-three patients initially diagnosed as CIN2+ were recruited. Data on immunohistochemical (IHC) staining scores, along with demographic and clinical information were collected. Using least absolute shrinkage and selection operator (LASSO) regression analysis, variables were identified for inclusion. A predict model and nomogram were developed through multi-factor logistic regression. The goodness-of-fit test was applied across different cohorts to construct the calibration curve of the model, and the predictive effect was evaluated by the receiver operating characteristic curve. Decision curve analysis was performed to determine the net benefit. Results Five predictor variables, including protein expression score, vaginal infection, HPV coinfection, and cone height were screened and plotted as a nomogram. The calibration curves showed a good fit. The area under the curve of the model was 0.835 for the training cohort and 0.728 for the internal test cohort. The decision curve analysis indicated that the nomogram provides significant net advantages for clinical use. Conclusion A practical nomogram predict model was developed to predict abnormal follow-up outcomes in CINs after conization.

Associations Between Preoperative Inflammatory Indices and Residual or Recurrent Cervical Intraepithelial Neoplasia Post Loop Electrosurgical Excision Procedure

Associations Between Preoperative Inflammatory Indices and Residual or Recurrent Cervical Intraepithelial Neoplasia Post Loop Electrosurgical Excision Procedure

An integrated approach to secondary prevention of cervical intraepithelial neoplasia

Secondary prevention of cervical precancer is aimed at preventing recurrence of cervical intraepithelial neoplasia (CIN) after excisional treatment. Recurrence of CIN after surgical treatment occurs in 8.1–14.4% of cases, which increases the risk of developing cervical cancer (CC). Despite the high effectiveness of local surgical treatment of patients with high-grade intraepithelial lesions (HSIL), an increased risk of late diagnosis of cervical cancer has been proven in comparison with the risk in the general population. The review article presents current data on factors that increase the potential risk of recurrence of precancer. Human papillomavirus (HPV) persistence is considered one of the leading predictors of relapse of CIN2+, regardless of the type of excision treatment. The combination of persistent high-risk (HR) HPV and a positive sectional margin significantly increases the risk of persistent/recurrent CIN2+. A negative co-test after conization during follow-up contributes to a favorable prognosis and the development of HSIL is observed less frequently than in the population. Only an integrated approach, including detection of cervical HPV HR infection after excisional treatment of CIN, assessment of the radicality of resection and timely measures to eliminate ineffective treatment, as well as subsequent active monitoring of patients, allows avoiding its recurrence and progression of cervical precancer

A Random Survival Forest Model for Predicting Residual and Recurrent High-Grade Cervical Intraepithelial Neoplasia in Premenopausal Women.

Loop electrosurgical excision procedure (LEEP) for high-grade cervical intraepithelial neoplasia (CIN) carries significant risks of recurrence and persistence. This study compares the efficacy of a random survival forest (RSF) model with that of a conventional Cox regression model for predicting residual and recurrent high-grade CIN in premenopausal women after LEEP. Data from 458 premenopausal women treated for CIN2/3 at our hospital between 2016 and 2020 were analyzed. The RSF model incorporated demographic, pathological, and treatment-related variables. Feature selection utilizing LASSO and three other algorithms was performed to enhance the RSF model, which was further compared to a Cox regression model. Model performance was assessed using area under the curve (AUC), out-of-bag (OOB) error rates, and SHAP values to interpret predictor importance. The RSF model showed superior performance compared to the Cox regression model, with AUC values of 0.767-0.901 and peak predictive performance at 36 months post-LEEP. In contrast, the highest AUC achieved by Cox regression was 0.880. The RSF model also exhibited relatively lower OOB error rates, indicating better generalizability. Moreover, SHAP value analysis identified margin status and CIN severity as the most prominent predictors that directly affected risk predictions. Lastly, an online tool providing real-time predictions in clinical settings was successfully implemented using the RSF model. The RSF model outperformed the traditional Cox regression model in predicting residual and recurrent high-grade CIN risks post-LEEP. This model may be a more accurate clinical tool that facilitates improved personalized care and early interventions in gynecological oncology.

Pharmacological correction of immunological disorders in perimenopausal women with recurrent epithelial cervical dysplasia associated with human papillomavirus infection

Despite the successes achieved in implementing screening programs and treating diseases caused by human papillomavirus (HPV) infection, the frequency of cervical intraepithelial neoplasia (CIN) of moderate and high grades associated with high-risk human papillomavirus (HR-HPV) remains between 9% to 21%. Vaginal dysbiosis and the development of immunodeficient states due to persistent HR-HPV infection require effective immunomodulatory and antiviral therapy before cervical surgery in perimenopausal women with recurrent CIN II.The objective: to evaluate the effectiveness of antiviral and immunomodulatory therapy by determining the state of vaginal biocenosis, immunological status and papillomavirus load of the cervical mucosa before surgical treatment in perimenopausal women with recurrent CIN II.Materials and methods. A prospective study was conducted on 98 women aged 40 to 55 years old, including 60 patients with morphologically verified recurrent CIN II associated with high-risk HPV, forming the main group. The control group comprised 38 women with negative HPV test results and without significant gynecological or somatic pathology. In the main group, a complex consisting of a blend of plant extracts of sod pike grass (Deschampsia caespitosa), ground cinquefoil grass (Calamagrostis epigeios), and echinacea purpurea grass (Echinaceae purpureae) was administered orally.Vaginal microbiota was assessed using Hey-Іson criteria, and immunological status was examined in patients using solid-phase enzyme-linked immunosorbent assay to determine IgG, IgM, IgA antibodies in serum and cervical mucus, levels of interleukin-1β (IL-1β), interferons alpha (IFN-α), gamma (IFN-γ), tumor necrosis factor alpha (TNF-α). Additionally, the DNA of high-risk HPV in cervical mucosa was quantitatively assessed using real-time PCR. The investigations were conducted before and after the applied therapy.Results. The investigation of vaginal content revealed the presence of bacterial vaginosis in 65.0% of patients in the main group, the frequency of which decreased by 2 times after treatment, with the number of women with an intermediate type of vaginal content increasing by 2.8 times (51.7%) and those with normal microbiota increasing by 2.5 times. Disruptions in cellular and humoral immunity systems were identified. After treatment, there was an increase in viral load in the significant «threshold» category (3–5 lg) by 1.25 times and in the «above threshold for progression» category (>5 lg) by 2.3 times, reflecting natural HPV clearance. No direct correlation was found between viral load activity and the degree of CIN or positive morphological changes regarding regression of cervical intraepithelial lesions.Conclusions. The use of a complex containing a blend of plant extracts of sod pike grass (Deschampsia caespitosa), ground cinquefoil grass (Calamagrostis epigeios), and echinacea purpurea grass (Echinacea purpureae) improves the state of vaginal biocenosis, indicators of cellular and humoral immunity, and promotes HPV elimination, it has adequate safety and tolerability, which determines the feasibility of its use in the complex treatment of cervical intraepithelial neoplasia at the preparatory stage before surgery and in the postoperative period to prevent complications and relapses.

Inflammatory Markers in Prior Loop Electrosurgical Excision Procedure (LEEP) as a Prognosis Factor in the Recurrence of Cervical Intraepithelial Neoplasia.

To investigate the relationship between preoperative inflammatory markers and recurrence of CIN after loop electrosurgical excision procedure (LEEP). A retrospective historical cohort study was conducted at gynecologic oncology unit, Bhumibol Adulyadej Hospital, Royal Thai Air Force, Thailand. Data was collected from medical records of CIN cases from year 2016 to 2021. Inclusion criteria were subjects who were diagnosed of CIN and underwent LEEP with pathologic confirmation and followed up for two years (at 6 months, 1 year, and 2 years). Preoperative complete blood count (CBC) was obtained within one month for calculation as systemic inflammatory values. One hundred and ten cases of CIN were enrolled. Mean age of participants was 48.1 years old. Three-fourths (83/110) of the participants had histological confirmation as CIN2/3. Sixteen (18/110) and twenty (22/110) percentage of cases had recurrence of disease at 1 and 2 years, respectively. Monocytes /lymphocytes ratio (MLR) and systemic inflammation response index (SIRI) could predict recurrence of CIN within 2 years. MLR more than 0.16 and SIRI more than 0.57 gave the sensitivity and negative predictive value (NPV) at percentage of 77.3/ 81.8 and 91.8/ 90.2, respectively. Combination of MLR and SIRI had sensitivity and NPV at 90.5 and 95.4 percent, respectively. MLR and SIRI could not predict marginal involvement, glandular involvement, and LEEP confirmed CIN 2/3. Pretreatment MLR and SIRI were statistically significant in predicting the recurrence in CIN after post LEEP procedure within 2 years follow up.

Topical imiquimod treatment of residual or recurrent cervical intraepithelial neoplasia lesions (TOPIC-2): A randomised controlled trial.

To investigate the efficacy of imiquimod in women with residual or recurrent cervical intraepithelial neoplasia (rrCIN), compared with large loop excision of the transformation zone (LLETZ). Randomised controlled non-inferiority trial. One academic and one regional hospital in the Netherlands. Thirty-five women with rrCIN were included in the study between May 2016 and May 2021. Women were randomised to receive treatment with 5% imiquimod cream (12.5 mg) intravaginally (three times a week for a duration of 16 weeks) or a LLETZ procedure (standard treatment). The primary outcome was reduction to normal cytology at 6 months after starting treatment. Secondary outcomes were clearance of high-risk human papilloma virus (hr-HPV) in both groups and reduction to ≤CIN1 in the imiquimod group. Side effects were monitored. Treatment success was 33% (6/18) in the imiquimod group versus 100% (16/16) in the LLETZ group (P < 0.001), whereas HPV clearance was 22% (4/18) in the imiquimod group versus 88% (14/16) in the LLETZ group (P < 0.001). After the randomisation of 35 women, the futility of treatment with imiquimod was proven and the trial was prematurely finished. In the follow-up period, three patients remained without additional treatment, whereas all other patients underwent LLETZ, conisation or hysterectomy. In the LLETZ group none of the patients received additional treatment during 2 years of follow-up. This is the first randomised controlled trial to show that topical imiquimod has a significantly lower success rate in terms of reduction to normal cytology and hr-HPV clearance, compared with LLETZ, in women with rrCIN. Additionally, imiquimod has numerous side effects and after using imiquimod most women with rrCIN still required additional surgical treatment.

Logistic regression analysis of mRNA expression changes and prognosis after cervical surgery

Objective: The aim of this study was to investigate the diagnostic value of HPV (human papillomavirus) E6/E7 mRNA combined with thin-layer liquid-based cytology test (TCT) detection in patients with cervical intraepithelial neoplasia (CIN) in the residual and recurrence of lesions after cervical conization. Methods: A total of 154 patients who had undergone cervical conization and were diagnosed with high-grade cervical intraepithelial neoplasia (CIN 1 and CIN 3) by histopathology and had complete follow-up data were enrolled. TCT, HPV-DNA detection, and HPV E6/E7 mRNA detection combined with TCT detection in 12 months can be used to detect abnormal cytology (&amp;gt;atypical squamous epithelium of undetermined significance). Patients with atypical squamous cell of undetermined significance or high-risk HPV-DNA (+) or HPV E6/E7 mRNA combined with TCT (+) underwent colposcopy and cervical biopsy again for pathological diagnosis. Results: There were 9 cases of residual lesions and 22 cases of recurrence. Thirty of the 57 cases with positive HPV-DNA after surgery were still there or came back. Of the 26 cases with positive HPV E6/E7 mRNA combined with TCT, 24 were still there or came back. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy rate of HPV-DNA detection were 96.8%, 78.0%, 52.6%, 99.0%, and 81.8%, respectively; the sensitivity and specificity of HPV E6/E7 mRNA were combined with TCT detection of sex. Conclusion: HPV E6/E7 mRNA combined with TCT detection can be included in follow-up examinations, which can timely and effectively predict the risk of CIN residual or recurrence after cervical conization and reduce excessive examination and treatment.

Machine Learning Prediction of Residual and Recurrent High-Grade CIN Post-LEEP.

This study aims to develop a machine learning (ML) model to predict the risk of residual or recurrent high-grade cervical intraepithelial neoplasia (CIN) after loop electrosurgical excision procedure (LEEP), addressing a critical gap in personalized follow-up care. A retrospective analysis of 532 patients who underwent LEEP for high-grade CIN at Cangzhou Central Hospital (2016-2020) was conducted. In the final analysis, 99 women (18.6%) were found to have residual or recurrent high-grade CIN (CIN2 or worse) within five years of follow-up. Four feature selection methods identified significant predictors of residual or recurrent CIN. Eight ML algorithms were evaluated using performance metrics such as AUROC, accuracy, sensitivity, specificity, PPV, NPV, F1 score, calibration curve, and decision curve analysis. Fivefold cross-validation optimized and validated the model, and SHAP analysis assessed feature importance. The XGBoost algorithm demonstrated the highest predictive performance with the best AUROC. The optimized model included six key predictors: age, ThinPrep cytologic test (TCT) results, HPV classification, CIN severity, glandular involvement, and margin status. SHAP analysis identified CIN severity and margin status as the most influential predictors. An online prediction tool was developed for real-time risk assessment. This ML-based predictive model for post-LEEP high-grade CIN provides a significant advancement in gynecologic oncology, enhancing personalized patient care and facilitating early intervention and informed clinical decision-making.

Optimising follow-up strategy based on cytology and human papillomavirus after fertility-sparing surgery for early stage cervical cancer: a nationwide, population-based, retrospective cohort study

The optimal follow-up strategy to detect recurrence after fertility-sparing surgery for early stage cervical cancer is unknown. Tailored surveillance based on individual risks could contribute to improved efficiency and, subsequently, reduce costs in health care. The aim of this study was to establish the predictive value of cervical cytology and high-risk human papillomavirus (HPV) testing to detect recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+; including recurrent cervical cancer) after fertility-sparing surgery. In this nationwide, population-based, retrospective cohort study, we used data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank. All patients aged 18-40 years with cervical cancer of any histology who received fertility-sparing surgery (ie, large loop excision of the transformation zone, conisation, or trachelectomy) between Jan 1, 2000, and Dec 31, 2020, were included. Pathology data from diagnosis, treatment, and during follow-up were analysed. The primary and secondary outcomes were the cumulative incidence of recurrent CIN2+ and recurrence-free survival, overall and stratified by results for cytology and high-risk HPV. 1548 patients were identified, of whom 1462 met the inclusion criteria. Of these included patients, 19 568 pathology reports were available. The median age at diagnosis was 31 years (IQR 30-35). After a median follow-up of 6·1 years (IQR 3·3-10·8), recurrent CIN2+ was diagnosed in 128 patients (cumulative incidence 15·0%, 95% CI 11·5-18·2), including 52 patients (cumulative incidence 5·4%, 95% CI 3·7-7·0) with recurrent cervical cancer. The overall 10-year recurrence-free survival for CIN2+ was 89·3% (95% CI 87·4-91·3). By cytology at first follow-up visit within 12 months after fertility-sparing surgery, 10-year recurrence-free survival for CIN2+ was 92·1% (90·2-94·1) in patients with normal cytology, 84·6% (77·4-92·3) in those with low-grade cytology, and 43·1% (26·4-70·2) in those with high-grade cytology. By high-risk HPV status at first follow-up visit within 12 months after surgery, 10-year recurrence-free survival for CIN2+ was 91·1% (85·3-97·3) in patients who were negative for high-risk HPV and 73·6% (58·4-92·8) in those who were positive for high-risk HPV. Cumulative incidence of recurrent CIN2+ within 6 months after any follow-up visit (6-24 months) in patients negative for high-risk HPV with normal or low-grade cytology was 0·0-0·7% and with high-grade cytology was 0·0-33·3%. Cumulative incidence of recurrence in patients positive for high-risk HPV with normal or low-grade cytology were 0·0-15·4% and with high-grade cytology were 50·0-100·0%. None of the patients who were negative for high-risk HPV without high-grade cytology, at 6 months and 12 months, developed recurrence. Patients who are negative for high-risk HPV with normal or low-grade cytology at 6-24 months after fertility-sparing surgery, could be offered a prolonged follow-up interval of 6 months. This group comprises 80% of all patients receiving fertility-sparing surgery. An interval of 12 months seems to be safe after two consecutive negative tests for high-risk HPV with an absence of high-grade cytology, which accounts for nearly 75% of all patients who receive fertility-sparing surgery. KWF Dutch Cancer Society.

P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIV.

The expression of p16 protein, a surrogate marker for high-risk human papillomavirus (hrHPV), is associated with cervical dysplasia. We evaluated correlates of p16 expression at treatment for high-grade cervical lesions and its utility in predicting the recurrence of cervical intraepithelial lesions grade 2 or higher (CIN2+) following cryotherapy among women with HIV. This is a subgroup analysis of women with HIV in Kenya with baseline cervical biopsy-confirmed CIN2+ who were randomized to receive cryotherapy and followed every six-months for two-years for biopsy-confirmed recurrence of CIN2+. P16 immunohistochemistry was performed on the baseline cervical biopsy with a positive result defined as strong abnormal nuclear expression in a continuous block segment of cells (at least 10-20 cells). Among the 200 women with CIN2+ randomized to cryotherapy, 160 (80%) had a baseline cervical biopsy specimen available, of whom 94 (59%) were p16-positive. p16 expression at baseline was associated with presence of any one of 14 hrHPV genotypes [Odds Ratio (OR) = 3.2; 95% Confidence Interval (CI), 1.03-9.78], multiple lifetime sexual partners (OR = 1.6; 95% CI, 1.03-2.54) and detectable plasma HIV viral load (>1,000 copies/mL; OR = 1.43; 95% CI, 1.01-2.03). Longer antiretroviral therapy duration (≥2 years) at baseline had lower odds of p16 expression (OR = 0.46; 95% CI, 0.24-0.87) than <2 years of antiretroviral therapy. Fifty-one women had CIN2+ recurrence over 2-years, of whom 33 (65%) were p16-positive at baseline. p16 was not associated with CIN2+ recurrence (Hazard Ratio = 1.35; 95% CI, 0.76-2.40). In this population of women with HIV and CIN2+, 41% of lesions were p16 negative and baseline p16 expression did not predict recurrence of cervical neoplasia during two-year follow up.

Factors Predicting Recurrence of Cervical Intraepithelial Neoplasia after Excisional Procedure-A 10-year Experience from A Tertiary Care Center

Factors Predicting Recurrence of Cervical Intraepithelial Neoplasia after Excisional Procedure-A 10-year Experience from A Tertiary Care Center

Timing of HPV vaccination as adjuvant treatment of CIN2+ recurrence in women undergoing surgical excision: a meta-analysis and meta-regression

ObjectiveThe main aim was to determine the overall vaccine effectiveness (VE) against recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+) including specific VE associated with timing of human papillomavirus...

Methylation testing for the detection of recurrent cervical intraepithelial neoplasia.

Women treated for CIN2/3 remain at increased risk of recurrent CIN and cervical cancer, and therefore posttreatment surveillance is recommended. This post hoc analysis evaluates the potential of methylation markers ASCL1/LHX8 and FAM19A4/miR124-2 for posttreatment detection of recurrent CIN2/3. Cervical scrapes taken at 6 and 12 months posttreatment of 364 women treated for CIN2/3 were tested for methylation of ASCL1/LHX8 and FAM19A4/miR124-2 using quantitative multiplex methylation-specific PCR. Performance of the methylation tests were calculated and compared with the performance of HPV and/or cytology. Methylation levels of recurrent CIN were compared between women with a persistent HPV infection, and women with an incident HPV infection or without HPV infection. Recurrent CIN2/3 was detected in 42 women (11.5%), including 28 women with CIN2 and 14 with CIN3. ASCL1/LHX8 tested positive in 13/14 (92.9%) of recurrent CIN3 and 13/27 (48.1%) of recurrent CIN2. FAM19A4/miR124-2 tested positive in 14/14 (100%) of recurrent CIN3 and 10/27 (37.0%) of recurrent CIN2. Combined HPV and/or methylation testing showed similar positivity rates as HPV and/or cytology. The CIN2/3 risk at 12 months posttreatment was 30.8% after a positive ASCL1/LHX8 result at 6 months posttreatment. Methylation levels of CIN2/3 in women with a persistent HPV infection were significantly higher compared with women with an incident or no HPV infection. In conclusion, posttreatment monitoring by methylation analysis of ASCL1/LHX8 and FAM19A4/miR124-2 showed a good performance for the detection of recurrent CIN. DNA methylation testing can help to identify women with recurrent CIN that require re-treatment.

Peculiarities of the vagina microbiome and functional activity of epithelial cells in cervical intraepithelial neoplasia of the cervix in women of perimenapausal age

According to the data of the National Cancer Registry of Ukraine for 2021, the incidence of cervical cancer was 17.9 and the mortality rate was 7.9 per 100,000 female population. Therefore, in modern conditions, timely diagnosis, effective treatment and prevention of precancerous processes, which include cervical intraepithelial neoplasia (CIN) of the cervix, is one of the important tasks of a gynecologist. Women in perimenopause, who are traditionally considered to be at risk, deserve special attention.Today, there is information in the literature that multifactorial diseases account for 90–95% of all diseases, including cervical cancer. Epidemiological factors associated with human papillomavirus (HPV) prevalence are well known. The role of microbial-protozoan-viral associations in contributing to the occurrence of intraepithelial lesions and cervical cancer is being actively investigated.The objective: to assess the state of microbiocenosis and the functional activity of epithelial cells in perimenopausal women with recurrent CIN of the cervix.Materials and methods. 60 women of perimenopausal age with recurrent CIN of the cervix, which occurred after treatment with surgical methods (main group) and 38 healthy women of the appropriate age (control group) were examined. All patients were examined in accordance with the regulatory orders of the Ministry of Health of Ukraine, immunological studies, as well as determination of the electrokinetic activity of epithelial cells of the vagina and cervix according to the method of V. I. Shakhbazov in modification of V. O. Beniuk and co-authors.Results. The data of the anamnesis and clinical examination of the patients were evaluated, which allows to identify a risk group among women of perimenopausal age, according to the development of recurrent CIN of the cervix. During the study of the species composition of the vaginal microbiome in patients of the main group, a decrease in the number or complete absence of lactobacilli, a predominance of opportunistic vaginal flora in the cases with HPV infection was established. Peptostreptococci were found in 46.7 %, corynebacterial – in 61.7%, epidermal staphylococcus – in 66.7%, gardnerella – in 53.3%, Candida spp. – in 46.7% of cases and some specific pathogens versus the control group (7.9%, 23.7%, 10.5%, 15.8%, 5.3%, respectively). Also, in the main group, a significant decrease in the level of interferon-α (IFN) by 1.6 and IFN-γ by 1.9 times in blood serum was found.Studies of the electrokinetic activity of the epithelial cells of the vagina and cervix revealed a decrease of more than 2 times the corresponding indicators in the main group compared to the control group.Conclusions. In perimenopausal women with recurrent CIN of the cervix, profound violations of the vaginal microbiocenosis with the predominance of opportunistic flora, as well as insufficiency of interferonogenesis, decreased functional activity of epithelial cells, were determined.In general, based on the results of this study and modern scientific data, it can be concluded that the association of HPV with a violation of the vaginal microbiome in the conditions of physiological menopausal changes significantly increases the risk of development and recurrence of cervical intraepithelial lesions in women. Therefore, the existing screening methods and modern management of diagnosis of CIN of the cervix are important for the provision of high-quality medical care.

Risk factors for recurrence of cervical intraepithelial neoplasia after loop electrosurgical excisional procedure in patients with positive margins.

Loop electrosurgical excisional procedure (LEEP) is a major treatment method for cervical precancerous lesions. However, recurrence rates were estimated to be 15%, and the risk is increased if a surgical margin is involved by dysplastic cells. This study aimed to identify the risk factors for recurrence of cervical precancerous lesions in patients with positive margins. We retrospectively reviewed medical records of patients who underwent LEEP between 2012 and 2014 and had a positive surgical margin. Clinicopathologic factors were collected, including age, parity, menopausal status, smoking, human papilloma virus infection, results of cytology/biopsy/LEEP, and specimen size and volume. A total of 117 patients with positive margins were included, and 26 (22.2%) patients had recurrence. According to a multivariate analysis, the recurrence rates were significantly higher in parous women (adjusted hazard ratio [HR], 2.92; 95% confidence interval [CI], 1.00-8.49), but positive margins at the exocervix (adjusted HR, 0.39; 95% CI, 0.17-0.91) and volume ≥4000 mm3 (adjusted HR, 0.36; 95% CI, 0.16-0.82) showed negative correlation. The risk of recurrence for cervical precancerous lesions increased in patients with a history of previous delivery, positive margin at the endocervix, and specimen volume of LEEP <4000 mm3 . These results could help gynecologists determine optimal treatment options for patients with positive margins.

The 5-year risk of recurrence of grade 2/3 cervical intraepithelial neoplasia after treatment in a population screening programme by human papillomavirus status: A cohort study in central Italy.

(a) To estimate the risk of recurrent cervical intraepithelial neoplasia, grade 2/3 or worse (CIN2+/CIN3+), lesions within 5 years of follow-up in human papillomavirus-negative/human papillomavirus-positive cohorts; (b) to assess whether certain risk factors can predict the recurrence of CIN2+/CIN3+ lesions; and (c) to provide recommendations for follow-up after treatment of cervical intraepithelial neoplasia, grade 2/3 to prevent cervical cancer. Organized cervical cancer screening programme in Central Italy. We included 1063 consecutive first excisional treatments performed between 2006 and 2014 for screening-detected cervical intraepithelial neoplasia, grade 2/3 lesions among women aged 25-65. The study population was divided into two groups according to the human papillomavirus test results performed 6 months after treatment: Human papillomavirus-negative and human papillomavirus-positive cohorts. The 5-year risk of developing cervical intraepithelial neoplasia, grade 2/3 or worse (CIN2+/CIN3+) was estimated using the Kaplan-Meier method and the Cox regression model. Among 829 human papillomavirus-negative and 234 human papillomavirus-positive women, six (0.72%; three cervical intraepithelial neoplasia, grade 2, three cervical intraepithelial neoplasia, grade 3) and 45 (19.2%; 15 cervical intraepithelial neoplasia, grade 2, 30 cervical intraepithelial neoplasia, grade 3), respectively, developed CIN2+ recurrence within 5 years of follow-up. The cumulative risks for CIN2+ and CIN3+ were 0.9% (95% confidence interval: 0.4%-2.0%) and 0.5% (95% confidence interval: 0.1%-1.4%), respectively, for the human papillomavirus-negative cohort, and 24.8% (95% confidence interval: 18.5%-32.7%) and 16.9% (95% confidence interval: 11.4%-24.5%), respectively, for the human papillomavirus-positive cohort. Risk factors associated with increased risk of recurrence were both margins positive for the human papillomavirus-negative cohort, and positive margins, cervical intraepithelial neoplasia, grade 3 lesions, high-grade cytology and high viral load for the human papillomavirus-positive cohort. Human papillomavirus testing can identify women at increased risk of recurrence and this supports a recommendation for its use in the post-treatment follow-up of cervical intraepithelial neoplasia, grade 2/3 lesions.

The efficacy of human papillomavirus prophylactic vaccination after conization in preventing cervical intraepithelial neoplasia recurrence: A prospective observational study in China

High-risk human papillomavirus (hrHPV) infection is the cause of most cervical cancers. Since therapeutic vaccines are not yet available for clinical practice, the administration of HPV prophylactic vaccines in patients with cervical intraepithelial neoplasia (CIN) arouses great interest and its value after excisional treatment of CIN remains unclear. We conducted this prospective cohort study to evaluate the impact of HPV prophylactic vaccination on preventing women from subsequent infection and cervical lesions after excision treatment. 148 patients after loop electrosurgical excision procedure (LEEP) for CIN2+ disease received HPV prophylactic vaccination (6/11/16/18 vaccine, Gardasil®, Merck) after surgery (V-group) and 273 didn’t get vaccination (NV-group). The HPV infection rates at the first and second year after LEEP were significantly lower in the V-group than that in NV-group (P = 0.049 and P = 0.026). CIN2+ recurrence was observed in 29 cases (10.62 %) in the NV-group and 2 cases (2.03 %) in the V-group. Logistic regression analysis showed that the HPV16/18 infection, the CIN3 pathology after LEEP and no vaccination after LEEP were significant risk factors of recurrence. Patients without HPV vaccination had a higher CIN2+ recurrence rate (OR = 12.35, 95 % CI 1.919–79.492, P = 0.008). Our study showed the quadrivalent prophylactic HPV vaccination after LEEP had a significantly protective role in the prevention of high-grade squamous intraepithelial lesion recurrence. Further randomized, controlled trials are required in elucidating the efficacy of the prophylactic HPV vaccines using shortly after LEEP in patients with CIN disease.

Adjuvant Human Papillomavirus Vaccination After Excisional Procedure for Cervical Intraepithelial Neoplasia: A Cost-Effectiveness Analysis.

To examine the cost effectiveness of human papillomavirus (HPV) vaccination after excisional procedure compared with no vaccination. We constructed a decision-analytic model (TreeAge Pro 2021) to compare outcomes between patients who underwent an excisional procedure followed by nonavalent HPV vaccination to those who underwent an excisional procedure without vaccination. Our theoretical cohort contained 250,000 patients, the approximate number undergoing excisional procedures annually in the United States. Our outcomes were costs, quality-adjusted life-years (QALYs), recurrence events, number of surveillance Pap tests with co-testing, number of colposcopies, and second excisional procedures. Probabilities of recurrence were based on a recently published meta-analysis. All values were derived from the literature, and QALYs were discounted at a rate of 3%. Outcomes were applied for 4 years after the initial excisional procedure. Our cost-effectiveness threshold was $100,000 per QALY. Sensitivity analyses were performed to evaluate the robustness of the model. In our theoretical cohort of patients who underwent an excisional procedure, the HPV vaccination strategy was associated with 17,281 fewer recurrences of cervical intraepithelial neoplasia (CIN) (8,360 fewer cases of CIN 1 and 8,921 fewer cases of CIN 2 or 3), 26,203 fewer Pap tests (1,025,368 vs 1,051,570), 17,281 fewer colposcopies (20,588 vs 37,869), and 8,921 fewer second excisional procedures (4,779 vs 13,701). The vaccination strategy was associated with a higher cost of $135 million. Vaccination was a cost-effective strategy, with an incremental cost-effectiveness ratio of $29,181 per QALY, compared with no vaccination. In our sensitivity analyses, the HPV vaccination strategy remained cost effective until the cost of the three-dose HPV vaccine series reached $1,899 or the baseline (nonvaccinated) probability of recurrence was less than 4.8%. In our model, HPV vaccination for patients with a prior excisional procedure led to improved outcomes and was cost effective. Our study suggests that clinicians should consider offering the three-dose HPV vaccine series to patients who have undergone an excisional procedure to decrease the risk of CIN recurrence and its sequelae.

Predictors of recurrence of cervical intraepithelial neoplasia of high severity after treatment with excisional methods

Predictors of recurrence of cervical intraepithelial neoplasia of high severity after treatment with excisional methods