Treatment of cervical intraepithelial lesions

Precancerous cervical lesions precede the development of invasive cervical cancer by 10–20 years, making cervical cancer preventable if these lesions are detected and effectively treated. Treatment has evolved in the last few decades and now includes ablative options that can be performed in lower‐resource settings where surgical excision is not feasible or routinely available. Gas‐based cryotherapy, which freezes cervical tissue to induce localized necrosis, is the most commonly used ablative treatment. However, its implementation in low‐resource settings is difficult because the refrigerant gas can be difficult to procure and transport, and is expensive. New cryotherapy devices that do not require an external supply of gas appear promising. Thermal coagulation, which burns cervical tissue to induce necrosis, has become more widely available in the last few years owing to its portability and the feasibility of using battery‐powered devices. These two ablative treatments successfully eradicate 75%–85% of high‐grade cervical lesions and have minor adverse effects

Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment

BackgroundHuman papillomavirus vaccines prevent human papillomavirus infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an human papillomavirus-associated lesion is not fully understood.ObjectivesTo determine whether human papillomavirus-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions.Study DesignWe included 1711 women (18−25 years) with carcinogenic human papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted human papillomavirus-16/18 virus-like particle vaccine. Participants were randomized (human papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low-grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2 or greater. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated.ResultsMedian follow-up was 56.7 months (women with human papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human papillomavirus types present at enrollment. Vaccine efficacy for human papillomavirus 16/18 clearance and against human papillomavirus 16/18 progression from infection to cervical intraepithelial neoplasia 2 or greater were −5.4% (95% confidence interval −19,10) and 0.3% (95% confidence interval −69,41), respectively. Among treated women, 34.1% had oncogenic infection and 1.6% had cervical intraepithelial neoplasia 2 or greater detected after treatment, respectively, and of these 69.8% and 20.0% were the result of new infections. We observed no significant effect of vaccination on rates of infection/lesions after treatment. Vaccine efficacy estimates for human papillomavirus 16/18 associated persistent infection and cervical intraepithelial neoplasia 2 or greater after treatment were 34.7% (95% confidence interval −131, 82) and −211% (95% confidence interval −2901, 68), respectively. We observed evidence for a partial and nonsignificant protective effect of vaccination against new infections absent before treatment. For incident human papillomavirus 16/18, human papillomavirus 31/33/45, and oncogenic human papillomavirus infections post-treatment, vaccine efficacy estimates were 57.9% (95% confidence interval −43, 88), 72.9% (95% confidence interval 29, 90), and 36.7% (95% confidence interval 1.5, 59), respectively.ConclusionWe find no evidence for a vaccine effect on the fate of detectable human papillomavirus infections. We show that vaccination does not protect against infections/lesions after treatment. Evaluation of vaccine protection against new infections after treatment and resultant lesions warrants further consideration in future studies

Application and future perspective of trichloroacetic acid in the treatment of cervical intraepithelial neoplasia after cold knife conization

Background: Factors that contribute to development of cervical intraepithelial neoplasia are: age older than 55, and infection with persistent, high risk Human papillomavirus (HPV). If the HPV remains in an episomal nonintegrated state, it results with low grade lesion and if virus becomes integrated into the human genome, high grade lesions and cancer may develop. Low grade lesion is cervical intraepithelial neoplasia and it refers to mildly atypical cellular changes in the lower third of the epithelium. High grade cervical lesions are cervical intraepithelial neoplasia II and III. CIN II refers to moderately atypical cellular changes confined at the basal two thirds of the epithelium and CIN III refers to severely atypical cellular changes encompassing greater than two thirds of the epithelial thickness. Cold knife conization usually is the treatment of choice for high grade cervical lesions. Case report: We present a case of new creative treatment with 85% trichloroacetic acid, of low grade cervical intraepithelial neoplasia, which was a residual cervical lesion after a cold knife conization preformed for high grade cervical intraepithelial neoplasia grade treatment. Conclusion: Single topical use of 85% trichloroacetic acid is an effective treatment for residual persistent cervical intraepithelial neoplasia of low grade, after cold knife conization and provides long term remission and satisfying Human papillomavirus clearance. Thus 85% trichloroacetic acid treatment can directly diminish morbidity and mortality of Human papilloma virus related to precancerous cervical lesions and cervical carcinoma

Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy : multicentre randomised controlled trial

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Assessing the see-and-treat approach for the management of high-grade squamous intraepithelial cervical lesions

Objectives: To assess local histological outcomes in patients with HSIL cytology results on cervical smears, in both the see-and-treat and three-step approach. Study Design: A retrospective analysis of patients with HSIL on cervical cytology was performed, obtaining an 83 patient cohort. The histological result following the primary investigation (colposcopic-directed biopsy or excisional procedure) was noted for each patient together with their demographic variables and HPV status. Results: Of 83 patients with HSIL cytology on cervical smear, 43 underwent LLETZ as a primary procedure, while 40 patients underwent a colposcopic-directed biopsy. There was no statistically significant difference in terms of dermographics and HPV status between the two groups. In those patients who had LLETZ as a primary procedure, 29 had CIN2+ on histology. On the other hand, following colposcopic-directed biopsies, 17 resulted in CIN2+ on histology. Conclusion: The conventional approach within our local setting potentially has inferior sensitivity in picking up CIN2+ lesions when compared to the see-and-treat approach. On the other hand, primary excisional procedures were associated with an overtreatment rate of at least 20.9%, subjecting patients to unnecessary risks. Local improvement of colposcopic skill will aid to reduce this overtreatment rate and missed lesions at biopsy.peer-reviewe

Conservative surgical treatment in cervical dysplastic lesions associated with cystorectocele

The treatment of cervical intraepithelial neoplasia aims at removing the squamocolumnar junction area, including abnormal tissues, up to the healthy tissue. Old postpartum perineal tears associated with cystorectocele, hypertrophic cervical elongation, and first and second degree uterine prolapse are pelvic static disorders. Particular aspects of pelvic-genital static disorder are related to the vulnerability of the pelvic-perineal floor during birth. On the occasion of birth, especially when there are different forms of dystocia during labor, the degradation of soft pelvic, genital, and vaginal-perineal tissues can occur. The objective of this study was to re-evaluate the conservative treatment of cervical dysplasia, depending on the degree of cervical lesions, the surface extension, the age of the patients, and the pathology associated with cervical lesions – colpocele, cystorectocele, and urinary incontinence in the old postpartum perineal tears. In order to solve the three types of concomitant lesions, we used the Manchester operation: the anterior colporrhaphy with the recalibration of the urethra and the suspension of the cystocele, the minimal colpectomy, the lesional cervical amputation with the anterior fixation of the parameters, and the posterior colpoperineorrhaphy with high myorrhaphy of the levator ani muscles. The decision on the management of cervical dysplasia has taken into account the degree of cervical lesions, the extension on the surface, the patients’ age and the pregnancy planning, and the pathology associated with cervical lesions. The Manchester operation is a conservative surgical procedure, effective in women under 45 years old, multiparous, with present genital activity, with dysplastic cervical lesions and cystorectocele. It also solves cystorectocele, cervical dysplasia, hypertrophic cervical elongation, and first and second degree uterine prolapse

MicroRNA-551b expression profile in low and high-grade cervical intraepithelial neoplasia

OBJECTIVE: To evaluate the expression of microRNA (miR)-551b in patients with low and high grade cervical intraepithelial neoplasia (CIN) and to find an association with high-risk Human Papillomavirus (HR-HPV) infection-related prognostic biomarkers. PATIENTS AND METHODS: The expression level of miR-551b was determined in 50 paraffin-embedded cervical specimens (10 normal squamous epithelium, 18 condylomas, 8 CIN1, and 14 CIN2-3) using quantitative Real-time polymerase chain reaction (qRT-PCR). χ2-test compared miR-551b expression in different diagnosis groups. An Ordered Logistic Regression and a Probit correlation were made to correlate miR-551b expression levels with the cervical tissue histological findings. The immunohistochemical distribution of p16 and Ki-67 according to histopathological findings was also assessed. RESULTS: The distribution of the miR-551b expression profile was significantly lower in CIN1-3 samples compared to other histological diagnosis groups (condyloma and negative). The expression levels were inversely correlated to the cervical pathological grade, from negative to CIN2-3. A 1% increase in miR-551b expression level produced an increase of 19% to the probability of a minor histological grade diagnosis in a range from negative to CIN2-3 and an increase of 13% to the probability of a negative histological grade diagnosis. Among the cases with miR-551b expression < 0.02 (considered as cut-off value) a significant statistical correlation was found between p16 and Ki-67 expression and the diagnosis of CIN2-3. CONCLUSIONS: O ur d ata s howed a s ignificant inverse correlation between miR-551b expression and the histological grading of the lesions, suggesting a tumor suppressive function in the different stages of cervical dysplasia

High-grade vaginal intraepithelial neoplasia and risk of progression to vaginal cancer. a multicentre study of the Italian Society of Colposcopy and Cervico-Vaginal Pathology (SICPCV)

OBJECTIVE: The aim of this study was to analyse the women with high grade vaginal intraepithelial neoplasia (HG-VaIN), in order to identify a subset of women at higher risk of progression to invasive vaginal cancer. MATERIALS AND METHODS: The medical records of all the women diagnosed with HG-VaIN, and subsequently treated, from January 1995 to December 2013 were analyzed in a multicentre retrospective case series. The rate of progression to invasive vaginal cancer and the potential risk factors were evaluated. RESULTS: 205 women with biopsy diagnosis of HG-VaIN were considered, with a mean follow up of 57 months (range 4-254 months). 12 cases of progression to vaginal squamocellular cancer were observed (5.8%), with a mean time interval from treatment to progression of 54.6 months (range 4-146 months). The rate of progression was significantly higher in women diagnosed with VaIN3 compared with VaIN2 (15.4% vs. 1.4%, p < 0.0001). Women with HG-VaIN and with previous hysterectomy showed a significantly higher rate of progression to invasive vaginal cancer compared to non-hysterectomised women (16.7% vs. 1.4%, p < 0.0001). A higher risk of progression for women with VaIN3 and for women with previous hysterectomy for cervical HPV-related disease was confirmed by multivariable logistic regression analysis. CONCLUSIONS: A higher rate of progression to vaginal cancer was reported in women diagnosed with VaIN3 on biopsy and in women with previous hysterectomy for HPV-related cervical disease. These patients should be considered at higher risk, thus a long lasting and accurate follow up is recommended

Fertility and early pregnancy outcomes after conservative treatment for cervical intraepithelial neoplasia

BACKGROUND: Cervical intra-epithelial neoplasia (CIN) typically occurs in young women of reproductive age. Although several studies have reported the impact that cervical conservative treatment may have on obstetric outcomes, there is much less evidence for fertility and early pregnancy outcomes. OBJECTIVES: To assess the effect of cervical treatment for CIN (excisional or ablative) on fertility and early pregnancy outcomes. SEARCH METHODS: We searched in January 2015 the following databases: the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library, Issue 12, 2014), MEDLINE (up to November week 3, 2014) and EMBASE (up to week 52, 2014). SELECTION CRITERIA: We included all studies reporting on fertility and early pregnancy outcomes (less than 24 weeks of gestation) in women with a history of CIN treatment (excisional or ablative) as compared to women that had not received treatment. DATA COLLECTION AND ANALYSIS: Studies were classified according to the treatment method used and the fertility or early pregnancy endpoint. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effects model and inter-study heterogeneity was assessed with I(2). Two review authors (MK, AM) independently assessed the eligibility of retrieved papers and risk of bias. The two review authors then compared their results and any disagreements were resolved by discussion. If still unresolved, a third review author (MA) was involved until consensus was reached. MAIN RESULTS: Fifteen studies (2,223,592 participants - 25,008 treated and 2,198,584 untreated) that fulfilled the inclusion criteria for this review were identified from the literature search. The meta-analysis demonstrated that treatment for CIN did not adversely affect the chances of conception. The overall pregnancy rate was higher for treated (43%) versus untreated women (38%; RR 1.29, 95% CI 1.02 to 1.64; 4 studies, 38,050 participants, very low quality), although the inter-study heterogeneity was considerable (P < 0.01). The pregnancy rates in treated and untreated women with an intention to conceive (88% versus 95%, RR 0.93, 95% CI 0.80 to 1.08; 2 studies, 70 participants, very low quality) and the number of women requiring more than 12 months to conceive (14% versus 9%, RR 1.45, 95% CI 0.89 to 2.37; 3 studies, 1348 participants, very low quality) were no different. Although the total miscarriage rate (4.6% versus 2.8%, RR 1.04, 95% CI 0.90 to 1.21; 10 studies, 39,504 participants, low quality) and first trimester miscarriage rate (9.8% versus 8.4%, RR 1.16, 95% CI 0.80 to 1.69, 4 studies, 1103 participants, low quality) was similar for treated and untreated women, CIN treatment was associated with an increased risk of second trimester miscarriage, (1.6% versus 0.4%, RR 2.60, 95% CI 1.45 to 4.67; 8 studies, 2,182,268 participants, low quality). The number of ectopic pregnancies (1.6% versus 0.8%, RR 1.89, 95% CI 1.50 to 2.39; 6 studies, 38,193 participants, low quality) and terminations (12.2% versus 7.4%, RR 1.71, 95% CI 1.31 to 2.22; 7 studies, 38,208 participants, low quality) were also higher in treated women.The results should be interpreted with caution. The included studies were often small with heterogenous design. Most of these studies were retrospective and of low or very low quality (GRADE assessment) and were therefore prone to bias. Subgroup analyses for the individual treatment methods and comparison groups and analysis to stratify for the cone length was not possible. AUTHORS' CONCLUSIONS: This meta-analysis suggests that treatment for CIN does not adversely affect fertility, although treatment was associated with an increased risk of miscarriage in the second trimester. These results should be interpreted with caution as the included studies were non-randomised and many were of low or very low quality and therefore at high risk of bias. Research should explore mechanisms that may explain the increase in mid-trimester miscarriage risk and stratify this impact of treatment by the length of the cone and the treatment method used