Step-by-step laparoscopic excision of cervical stump for persistent CIN and bleeding in a postmenopausal patient without uterine manipulator

To assess human papilloma viruses (HPV) DNA test for detection of recurrences in cervical intraepithelial neoplasia (CIN) patients after loop electrosurgical excision procedure (LEEP). Also effect of LEEP on the clearance of HPV infection was evaluated for CIN 1 lesions. HPV DNA positive 37 patients (25 CIN 2-3 and 12 CIN 1 cases proven by colposcopic biopsies) were treated with LEEP and followed prospectively with HPV DNA and cytology at third and sixth months. There were 11 patients with abnormal cytologic results in third month and 4 in sixth month. HPV DNA positivity rate declined in CIN 1 group between third and sixth month but this did not reach to statistical significance (44 vs. 36%, P = 0.41). There were 3 treatment failures out of 37 patients (8.1%). All these three patients had CIN 3 at the beginning and two of them had positive HPV DNA in two controls. There were no recurrence/treatment failure for CIN 1 patients. Regarding 37 patients, decrease in cytologic abnormality incidence between third and sixth-month control was statistically significant (29.7 vs. 10.9%, P = 0.03). All four patients with cytologic abnormality at the sixth month had HPV persistence. Cytologic abnormality was more prevelant in HPV persistent women (P = 0.01) and also there was no cytologic abnormality in case of HPV DNA negativity. LEEP does not seem to decrease HPV DNA incidence for CIN 1 at least for 6 months. But HPV DNA used in addition to cytology might help to detect recurrences.

목적: 본 연구는 human papillomavirus (HPV) 감염과 클라미디아 감염이 자궁경부 이형성에 영향을 미치는지 알아보고자 하였다. 연구 방법: 자궁경부 액상세포진 검사에서 비정상으로 진단된 환자 374명을 대상으로 조직학적 검사와 HPV 및 클라미디아 감염의 상관관계를 연구하였다. 결과: 조직학적 검사결과 cervical intraepithelial neoplasia (CIN) 2가 16명, CIN 3가 55명, carcinoma in situ (CIS)가 53명이었으며 액상 세포진 검사에서는 atypical squamous cells of undetermined significance였으나 high-grade squamous intraepithelial lesions 이상인 고등급 병변이 22명이었으며, low-grade squamous intraepithelial lesions군에서도 7명이 고등급 병변으로 판정되었다. HPV 감염군은 235명이고 클라미디아 감염군은 31명(8.3%)이며, 두 군의 동시감염은 25명(6.7%)의 빈도를 보였으며 동시 감염군과 조직학적 병변의 악성도의 상관관계는 없었다(P=0.089). HPV 감염과 클라미디아 감염에는 선후 관계는 명확하지 않으나 P=0.022로 두 군 간에 유의한 상관관계가 존재한다고 볼 수 있다. 고등급 CIN군만을 대상으로 HPV 및 클라미디아 감염의 통계적 유의성은 P=0.157로 통계적 유의성은 없었으며, 고위험 HPV 감염과 클라미디아 감염 또한 P=0.195로 통계적 상관관계는 없었다. 결론: 자궁경부 상피내 종양 환자에서 HPV 감염은 그 역할이 널리 알려져 있으나 클라미디아 감염과의 연관성에 대해서는아직 더 많은 연구가 있어야 할 것으로 생각된다.

Objective To investigate the diagnosis and treatment of cervical intraepithelial neoplasia (CIN). Methods The clinical records and data of 200 patients with CIN diagnosed and treated in Shanxi Provincial People’s Hospital from January 2017 to January 2018 were retrospectively analyzed. All patients were diagnosed by three-step screening of the cervix, including thin-prep liquid-based cytology test (TCT) and/or human papilloma virus (HPV) detection, colposcopy and histopathology of the cervix. Loop electrosurgical excision procedure (LEEP) was performed according to patient’swillingness and HPV infection condition to diagnose cervix. For patients with cervical cancer diagnosed by patholgical examination, total laparoscopic extrafascial hysterectomy was performed. The TCT examination of cervix, colposcopy biopsy, operation and 1-year follow-up of all patients were observed. Results A total of 141 cases of low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) were detected by TCT of cervix among 200 CIN patients, and the diagnostic coincidence rate of TCT was 70.50%; while a total of 63 cases of CIN Ⅱ and CIN Ⅲ were detected by histopathology, and 45 cases of HSIL were detected by TCT, the diagnostic coincidence rate of TCT was 71.42%; 137 cases of CIN Ⅰ were detected by histopathology, 96 cases of LSIL were detected by TCT, and the diagnostic coincidence rate of TCT was 70.07%. A total of 163 cases of LSIL and HSIL were determined by colposcopy in 200 CIN patients, with the diagnostic accuracy of 81.50%; 63 cases of CIN Ⅱ and CIN Ⅲ were determined by histopathology, while 50 cases of HSIL were determined by colposcopy, with the diagnostic accuracy of 79.36%; 137 cases of CIN Ⅰ were determined by histopathology, and 113 cases of LSIL were determined by colposcopy, with the diagnostic accuracy of 82.48%. Among the 137 LSIL patients confirmed by histopathology, with cytological examination results showing cannot exlude high-grade squamous intraepithe lial lesion, aged over 45 years, and with lesions lasting for over 1 year, 52 patients underwent diagnostic LEEP operation. Among the 63 cases of HSIL confirmed by histopathology, 58 cases were treated by LEEP. Among the 63 HSIL patients, 5 patients with positive examination results in margin were given cytology + HPV + colposcopy every 6 months; and 4 of 5 patients were diagnosed as cervical cancer IA 1 stage by pathology, then the 4 patients were treated by total laparoscopic extrafascial hysterectomy after LEEP. Up to the end of 12-month follow-up, no CIN residue or cervical cancer recurrence was detected, but there were 8 cases of CIN recurrence. Conclusions Early diagnosis of precancerous cervical lesions and timely development of reasonable treatment are the key points to prevent and treat cervical cancer. Key words: Diagnosis; Precancerous cervical lesions; Treatment; Clinical analysis

To identify factors for predicting residual or recurrent cervical intraepithelial neoplasia (CIN) after cervical conization with negative margins. A total of 172 patients with histologically verified high-grade squamous intraepithelial lesions who underwent conization with negative margins were recruited at the General Hospital of Tianjin Medical University from December 2006 to January 2016. Follow-up comprised clinical examination, a liquid-based cytology test, a human papillomavirus (HPV) DNA genotyping test, colposcopy assessment, and if indicated, colposcopy-directed punch biopsy. The Kaplan-Meier method was used to analyze the median recurrent time, whereas log-rank tests and Cox regression models were used to determine the predictors of residual/recurrent CIN. Fourteen residual/recurrent cases (8.1%) were identified in 172 patients. In univariate analysis, cytologic abnormalities on follow-up (P = .000), conization method (P = .017), HPV positivity at any visit (P = .000), persistent HPV infection postconization (P = .000), persistent infection with the same HPV genotype (P = .000), and HPV positivity at 18 months after conization (P = .000) were predictive factors of residual/recurrent CIN. The results of multivariate analysis further revealed that persistent HPV infection postconization (P = .035), HPV positivity at 18 months after conization (P = .017), and cytologic abnormalities on follow-up (P = .000) had an increased risk of residual/recurrent CIN. During follow-up, patients with persistent HPV infection or cytologic abnormalities were at high risk of residual/recurrent CIN and should be identified for close surveillance and monitoring. Meanwhile, patients with HPV who became negative within 18 months after treatment had a low risk of recurrence.

BackgroundCervical cancer is caused by Human Papilloma viruses (HPV) and is preceded by precursor stages: Cervical Intraepithelial Neoplasia (CIN). CIN is mostly found in women in their reproductive age and treated with a Loop Electrosurgical Excision Procedure (LEEP). The recurrence or residual disease rate after treatment is up to 17%. These women have a lifelong increased risk of recurrent CIN, cervical cancer and other HPV related malignancies. Furthermore, LEEP treatments are associated with complications such as premature birth. Limited data show that prophylactic HPV vaccination at the time of LEEP reduces recurrence rates, therefore leading to a reduction in repeated surgical interventions and side effect like preterm birth.The primary study objective is to evaluate the efficacy of the nonavalent HPV vaccination in women with a CIN II-III (high-grade squamous intraepithelial lesion (HSIL) lesion who will undergo a LEEP in preventing recurrent CIN II-III after 24 months.MethodsThis study is a randomised, double blinded, placebo controlled trial in 750 patients without prior HPV vaccination or prior treatment for CIN and with histologically proven CIN II-III (independent of their hrHPV status) for whom a LEEP is planned. Included patients will be randomised to receive either three injections with nonavalent (9 HPV types) HPV vaccine or placebo injections (NaCL 0.9%) as a comparator. Treatment and follow-up will be according the current Dutch guidelines. Primary outcome is recurrence of a CIN II or CIN III lesion at 24 months. A normal PAP smear with negative hrHPV test serves as surrogate for absence of CIN. At the start and throughout the study HPV typing, quality of life and cost effectiveness will be tested.DiscussionAlthough prophylactic HPV vaccines are highly effective, little is known about the effectivity of HPV vaccines on women with CIN. Multiple LEEP treatments are associated with complications. We would like to evaluate the efficacy of HPV vaccination in addition to LEEP treatment to prevent residual or recurrent cervical dysplasia and decrease risks of repeated surgical treatment.Trial registrationMedical Ethical Committee approval number: NL66775.078.18. Affiliation: Erasmus Medical Centre. Dutch trial register: NL 7938. Date of registration 2019-08-05.

Factors associated with HPV persistence after treatment for high-grade cervical intra-epithelial neoplasia with large loop excision of the transformation zone (LLETZ)

Objective To explore the therapeutic effects of human papilloma virus (HPV) test combined with thinprep cytologic test (TCT) on evaluating loop electrosurgical excision procedure (LEEP) and the follow-up of high-grade cervical intraepithelial neoplasia(CIN). Methods From March 2005 to December 2006, 115 patients who subjected to loop electrosurgical excision procedure(LEEP) due to histologically confirmed cervical intraepithelial neoplasia(CIN) Ⅱ/Ⅲ were selected. They were classified into two groups according to the diagnosis, one of which was consisted of patients with cervical intraepithelial neoplasia Ⅱ(CINⅡ group, n=68, 59.13%), the other with cervical intraepithelial neoplasiaⅢ(including carcinoma in situ, CIN Ⅲ group, n=47, 40.87%). The study was according to the ethical standards enacted by the ethics committee and confirmed by the committee. Informed consent was obtained from all participates. All 115 cases who underwent loop excision procedure were followed-up until January 2008. Follow–up visits were consisted of cervical thinprep cytologic test during the following 4~6 months after the operation and hybrid capture Ⅱ (HC2) during the following 6~8 months. A retrospective analysis was performed to study effects and prognosis after loop electrosurgical excision procedure. Results The positive human papilloma virus rate was 95.74% in CIN Ⅲ group which was significantly higher than that in CIN Ⅱ group (73.53%) before loop electrosurgical excision(P 0.05). The sensitivity, specificity, positive predictive value(PPV), negative predictive value of hybrid capture Ⅱ were 66.67%, 98.12%, 57.14%, 98.15%. While the sensitivity, specificity, positive predictive value, negative predictive value of the thinprep cytologic test were 83.33%, 76.15%, 16.13%, 98.81%. Four cases whose hybrid capture Ⅱ and thinprep cytologic test both were positive showed residual or recurrent. Specificity and positive predictive value were significantly higher when two tests were combined. Conclusion Loop electrosurgical excision procedure is an effective way for treating high–grade cervical intraepithelial neoplasia. High risk human papilloma virus may play an important role in the occurrence of high grade cervical intraepithelial neoplasia. Pre–treatment of high risk human papilloma virus testing seems to have no predictive value for the prognosis of patients who undergo loop electrosurgical excision procedure for high–grade cervical intraepithelial neoplasia. High risk human papilloma virus combined with thinprep cytologic test during the post–treatment may be of great importance after loop electrosurgical excision procedure. Key words: cervical intraepithelial neoplasia (CIN); loop electrosurgical excision procedure (LEEP); human papilloma virus (HPV); thinprep cytologic test (TCT)

Cytology testing in the NHS Cervical Screening Programs in the United Kingdom has identified over a quarter of a million women with precancerous low-grade abnormalities (mild dyskaryosis or borderline nuclear abnormalities [BNA]). Some investigators have suggested that human papillomavirus (HPV) testing could help decide which of these women should be referred for colposcopy and which could safely be returned to routine recall. This multicenter randomized-controlled trial used data from a previous Trial Of Management of Borderline and Other Low-grade Abnormal smears Group (TOMBOLA) trial to determine whether an HPV test is useful among women with mild dyskaryosis or BNA in the choice between cytological surveillance and colposcopy, and after referral whether HPV testing is useful in choosing treatment (either immediate large loop excision of the transformation zone (LLETZ) or biopsy with selective recall. The study subjects were 4439 women, 20 to 59 years of age, with mild dyskaryosis or BNA at enrollment. HPV analysis was performed using the polymerase chain reaction assay with the GP5+/6+ general primer system. Both the study subjects and those involved in management were blinded to the HPV testing results. In the first of 2 randomizations, women were assigned to either cytological surveillance every 6 months or referral for immediate colposcopy. In the second randomization, women referred for colposcopy were assigned either to immediate LLETZ or biopsies with selective recall for LLETZ. Both randomizations were stratified for HPV status and age. In addition, the association between HPV status and the presence of cervical intraepithelial neoplasia (CIN) grade 2 or more severe disease (CIN2 or worse) was examined in women who underwent colposcopy. At the end of the 3-year follow-up, all women were invited for an exit examination, which included colposcopy. No significant interactions were found between management and HPV status, showing that HPV positivity among women with low-grade cytologic abnormalities at recruitment was not effective in the choice of immediate colposcopy over cytological surveillance (P = 0.76) or immediate LLETZ over biopsy and recall (P = 0.27). No difference was found between women with mild dyskaryosis and BNA in the sensitivity of a single HPV test in detection of CIN2 or worse, whereas specificity was higher in those with BNA (71.3%; 95% confidence interval [CI], 68.5%–74.1% vs. 46.9%; 95% CI, 42.2%–51.6%). With increasing age, the sensitivity decreased and the specificity increased. There was a high negative predictive value, especially among women with BNA (94.5%; 95% CI, 92.9%–96.0%). About 22% of women across all ages with CIN2 or worse were HPV negative. Conversely, 40% of HPV positive women did not have CIN. HPV was a more reliable predictor among women aged 40 or more compared with younger women. These findings indicate that a single HPV test may be useful in women over 40 years of age in determining which women with low-grade abnormal cytology should be referred for colposcopy, but may not be useful in women 40 years of age or less, or for determining the most effective management at colposcopy.

HPV vaccination following loop electrical excision procedure (LEEP) for cervical intraepithelial neoplasia: A cost-effectiveness analysis (134)

We performed a retrospective analysis of 204 patients who underwent large loop excision of the transformation zone (LLETZ) to determine whether women who have a negative LLETZ (no cervical intra-epithelial neoplasia (CIN) present) are at a lower risk of developing further abnormal cytology or CIN than women whose LLETZ is positive (CIN present). Overall 69 of the LLETZ samples were negative (34%) and 135 were positive (66%). The mean duration of negative cytology during follow up was 25·4 months (negative LLETZ) and 21·2 months (positive LLETZ) ( P =0·03). In the negative LLETZ group, cytology did not miss any cases of persistent CIN at the 6-month follow-up visit and 39 repeat punch biopsies were all negative. There were 3/69 cases (4·3%) in the negative LLETZ group and 13/135 (9·6%) in the positive LLETZ group of persistent disease (CIN diagnosed at or as a result of the 6-month follow-up). Following a negative 6-month review, one woman developed an abnormal smear in the negative LLETZ group (1/66=1·5%) compared with 10 women (10/122=8·1%) in the positive LLETZ group. Recurrent CIN (CIN subsequently diagnosed following a negative 6-month review) was seen in 0/69 cases (0%) in the negative LLETZ group and 4/135 (3·2%) in the positive LLETZ group. We conclude that women who undergo a negative LLETZ may represent a low-risk group for developing further cytological and histological abnormalities.

ObjectiveTo evaluate the efficacy of loop electrosurgical excision procedure (LEEP) combined with cold coagulation for treating cervical intraepithelial neoplasia (CIN).MethodsWe reviewed clinic-pathologic data of 498 patients treated with LEEP alone (n=354), and LEEP combined with cold coagulation (n=144) between January 2000 and December 2011. After LEEP, we followed up all patients by using Papanicolaou smear and human papillomavirus (HPV) test, and evaluated abnormal cervical cytology-free interval and high-risk HPV infection-free interval. Moreover, we investigated independent factors affecting abnormal cervical cytology or high-risk HPV infection after LEEP.ResultsAbnormal cervical cytology-free interval was longer in patients treated with LEEP combined with cold coagulation than in those treated with LEEP alone (mean, 92.4 vs. 84.4 months; P=0.01), and patients treated with LEEP combined with cold coagulation also showed longer high-risk HPV infection-free interval than those treated with LEEP alone (mean, 87.6 vs. 59.1 months; P=0.01). Moreover, CIN 3 and cold coagulation were factors affecting abnormal cervical cytology after LEEP (adjusted hazard ratios, 1.90 and 0.61; 95% confidence intervals, 1.27 to 2.84 and 0.39 to 0.96), and CIN 3, positive deep cervical margin and cold coagulation were also factors affecting high-risk HPV infection after LEEP (adjusted hazard ratios, 2.07, 4.11, and 0.64; 95% confidence intervals, 1.38 to 3.08, 1.63 to 10.39, and 0.43 to 0.96). When we performed subgroup analyses for patients with CIN 2 or CIN 3, the result were similar.ConclusionLEEP combined with cold coagulation may be more effective for treating CIN than LEEP alone. Moreover, cold coagulation may decrease the risk of potential of recurrence after LEEP.

We retrospectively analysed post-treatment human papillomavirus (HPV) results in women treated for cervical intraepithelial neoplasia (CIN) to establish if ‘virological cure’ rates achieved by cold coagulation matched those for large-loop excision of the transformation zone (LLETZ) in the treatment of CIN. The main outcome measure was the rate of non-detection of HPV at 6- and 18-month follow-up. HPV was not detected in 82.0% and 86.0% of women at 6- and 18-month follow-up, respectively. In women with high-grade CIN (CIN 2 or worse), there was no difference in HPV non-detection rates among the two treatment methods at six-month (81.8% for cold coagulation vs. 84.0% for LLETZ, χ2=0.23, p value=.632), and 18-month follow-up (83.3% for cold coagulation vs. 89.2% for LLETZ, χ2=1.46, p value=.227). Cervical cold coagulation provides a high ‘virological cure’ rate for all grades of CIN, equivalent to that seen with LLETZ.Impact StatementWhat is already known on this subject? It is well established that CIN cure rates after treatment with cold coagulation are comparable to those of excisional methods and are over 90% on cytological follow-up post-treatment. Furthermore, there are no demonstrable adverse effects on fertility and delivery in pregnancies conceived after cold coagulation according to long-term follow-up studies. In contrast, there is a positive correlation between treatment with LLETZ and the risk of subsequent subfertility and adverse pregnancy outcomes.What the results of this study add? This study provides evidence that cold coagulation achieves similar cure rates to that of LLETZ not only in cytology but also in HPV test of cure. This finding is significant as we are moving to a primary HPV cervical screening programme.What the implications are of these findings for clinical practice and/or further research? A negative high-risk HPV test provides a greater reassurance of a low risk of CIN 3 or cancer than a negative cytology result. Therefore, given parity to LLETZ in ‘virological cure’ rate and having no known adverse effects on fertility and pregnancy, cold coagulation should be used to treat most cases of CIN, especially in women of reproductive age.

The introduction of human papillomavirus (HPV) testing into cervical cancer screening programs has significantly improved the detection of premalignant lesions and continues to improve the detection and prevention of invasive cervical cancer. The results of 4 large trials successfully demonstrated higher detection rates of cervical intraepithelial neoplasia (CIN) 3 with HPV-based screening compared to cervical cytology [1,2,3,4,5], and a recent meta-analysis of long term follow up in those trials demonstrated 60% to 70% greater protection against invasive cancer compared to cytology screening [6]. While the role of HPV screening is well established with well-conducted randomized controlled trials, there are fewer consensuses regarding the utility of HPV testing after treatment for premalignant cervical lesions. Typically, CIN 2/3 lesions are treated with excisional or ablative procedures, and post-treatment these women are then entered into more intensive surveillance protocols. Post-treatment surveillance targets an important population, as women treated for CIN 2/3 have nearly a 300% greater risk of developing invasive cancer over the subsequent 20 years [7]. Two articles in this issue provide significant data to support the role of HPV testing after treatment for high-grade dysplasia. In human papillomavirus (HPV)-16 or HPV-18 genotype is a reliable predictor of residual disease in a subsequent hysterectomy following a loop electrosurgical excision procedure for cervical intraepithelial neoplasia 3, Kang et al. [8] evaluate 189 women who underwent a hysterectomy within 6 months of a loop electrosurgical excision procedure (LEEP) for CIN 3. They found residual disease in almost half of the women as well as early stage cancer in six patients. As expected, positive margins in the LEEP specimen were predictive of residual disease, but HPV viral load and HPV-16 or HPV-18 positivity were also predictive (p<0.01 and p<0.001, respectively). Based on their receiver operating characteristic curve for HPV viral load and predicting residual disease, a viral load of 220 relative light unit (RLU) could predict residual disease with 'a sensitivity of 65.2%, a specificity of 70.1%, and an accuracy of 67.7%.' In a multivariate analysis, the independent predictors of residual disease after LEEP were cone margin positivity, HPV viral load ≥220 RLU, positive endocervical cytology, and HPV-16 or HPV-18 positivity. Their data, including the use of hysterectomy specimen pathology provides short-term outcomes regarding residual or more advanced disease after LEEP for CIN 3 and demonstrates the clinical utility of HPV testing in this setting. Posttreatment human papillomavirus testing for residual or recurrent high-grade cervical intraepithelial neoplasia: a pooled analysis by Onuki et al. [9] utilizes different methodology to lend the same support to posttreatment screening. A systematic review of 33 articles published between 1996 and 2013 found 5,319 cases; each case had been treated for CIN 2/3+, was tested for HPV within 12 months, and documented the presence or absence of CIN 2/3+ in follow-up. The rate of CIN 2/3+, either recurrent or residual, was 8.4%. The sensitivity of HPV testing was significantly better than ASCUS+ cytology threshold (0.92 vs. 0.76). More importantly, the negative predictive value of HPV testing alone was 0.99 with a 95% CI of 0.99 to 1.00. In addition, the presence of disease at the excisional margin did not significantly affect the sensitivity or specificity of carcinogenic HPV testing. The authors evaluated both cytology and HPV testing alone and in combination, for risk stratification of residual/recurrent CIN 2/3+ after treatment for CIN 2/3+. They found the highest risk in HPV+/cytology+ women, followed by HPV+/cytology–, and finally HPV–/cytology+. Current guidelines in Japan and the UK recommend cytology alone during posttreatment follow-up for high-grade dysplasia [10,11]. United States guidelines recommend HPV testing for surveillance since 2012, albeit without level 1 evidence. However, the known pathogenesis and carcinogenic properties of HPV strongly support the use of HPV testing in this setting. The data presented in this issue by Kang et al. [8] and Onuki et al. [9] provide strong clinical evidence to support the use of HPV testing to evaluate risk for recurrent or residual high-grade dysplasia in patients previously treated for high-grade dysplasia. Their work continues to build on the library of data that demonstrate the utility and value of HPV testing in detecting cervical dysplasia and preventing cervical cancer.

The aims of the study were to estimate the rate and to identify predictors of high-grade abnormalities among women with persistent low-grade abnormalities or high-risk human papillomavirus (hrHPV) positivity for at least 2 years stratified by presence (high risk) or absence (low risk) of previous high-grade results or HPV 16/18. A retrospective cohort study of patients who underwent a loop electrosurgical excision procedure (LEEP) for persistent low-grade or hrHPV positivity was performed. Patients were stratified based on whether they had a history of high-grade and/or HPV 16/18 positivity. Rates of high-grade or worse abnormalities on LEEP were compared using Fisher exact tests. Logistic regression was used to evaluate the associations between patient characteristics and high-grade results on the LEEP. Three hundred eleven LEEPs were performed for persistent low-grade or hrHPV positivity. The rates of occult high grade were 12% and 22% among the low- and high-risk groups, respectively. Compared with those 45 years and older, the adjusted odds of high grade was 3.79 (95% CI = 1.19-12.1) for women aged 25-29 years. The odds of high grade was higher among current versus never smokers (6.40; 95% CI = 2.01-20.4) and those with a history of high-grade abnormality (2.23; 95% CI = 1.12-4.43). At 2 years, approximately half had an abnormal cytology and/or hrHPV positivity result independent of whether high grade was identified on their LEEP specimen. Patients with persistent low-grade abnormalities or persistent hrHPV should be counseled on the risks and benefits of a LEEP given that 12%-22% have a risk of occult high grade, especially if they have a history of high-grade dysplasia.

Objective To investigate the high risk factors of cervical adhesion caused by loop electrosurgical excision procedure (LEEP), and to find out the effective measures to prevent cervical adhesion caused by LEEP. Methods From January 2013 to December 2014, a total of 603 cases of menopausal transition and postmenopausal patients who received LEEP treatment in International Peace Maternity & Child Health Hospital of China Welfare Institute with taking cervical adhesion prevention measures after LEEP were enrolled into study group. From January 2003 to December 2012, a total of 10 863 cases of patients who received LEEP treatment in International Peace Maternity & Child Health Hospital of China Welfare Institute without taking cervical adhesion prevention measures after LEEP were enrolled into non-intervention group. According to the different cervical adhesion prevention measures after LEEP in study group: placing intrauterine device (IUD) which was T type ring with tail wire once after the treatment of LEEP or using Hegar cervical dilator for physical cervical dilatation, the menopausal transition and postmenopausal patients in study group were further divided into IUD subgroup (n=144) and physical dilator subgroup (n=459). And in the non-intervention group, the menopausal transition and postmenopausal women were included into control group (n=2 270). The incidence of cervical adhesion caused by LEEP in non-intervention group and the related risk factors of cervical adhesion caused by LEEP were analyzed by retrospective analysis method. By following up the study group, the effects of cervical adhesion intervention measures were analyzed prospectively. The incidences of cervical adhesion caused by LEEP in study group and control group, and the incidences of cervical adhesion caused by LEEP and genital tract infection in IUD subgroup and physical dilator subgroup were statistically compared to evaluate the effects of the cervical adhesion intervention measures. There were no statistical differences between the study group and control group, IUD subgroup and physical dilator subgroup in the basic data such as age, gravidity and parity, ratio of type of disease, mode of delivery and so on (P>0.05). Results ①The incidence of cervical adhesion caused by LEEP in non-intervention group was 9.6% (1 042/10 863). In non-intervention group, the incidences of cervical adhesion caused by LEEP in the patients with menopausal transition and menopause, previous cesarean section delivery and conization depth >10 mm were obviously higher than those in the patients with mature period, the previous vaginal delivery, conization depth 0.05). ②The incidence of cervical adhesion caused by LEEP in study group was 10.6% (64/603), which was significantly lower than that in control group (43.8%, 995/2 270), and the difference was statistically significant (χ2=225.90, P<0.001). The incidences of cervical adhesion caused by LEEP in IUD subgroup and physical dilator subgroup were 18.1% (26/144) and 8.3% (38/459), respectively, and they were both obviously lower than that in control group, and both the differences were statistically significant (χ2=36.87, P<0.001; χ2=205.16, P<0.001). The incidences of cervical adhesion caused by LEEP in physical dilator subgroup was obviously lower than that in IUD subgroup, and the difference was statistically significant (χ2=11.04, P<0.001). ③In IUD subgroup, the expulsion rate of IUD was 41.0% (59/144). The genital tract infection rate in IUD subgroup was 24.3% (35/144), which was significantly higher than that in physical expansion subgroup (8.5%, 39/459), and the difference was statistically significant (χ2=25.45, P<0.001). Conclusions The three high risk factors of cervical adhesion caused by LEEP are menopause, delivery mode and conization depth. Both IUD and Hegar cervical dilator can significantly reduce the incidence of cervical adhesion caused by LEEP, but physical dilator method is better and more effective than IUD, and IUD is easy to fall off and the genital tract infection rate is higher than physical dilator method, so physical dilatation of the cervix is a more economical and effective method for the prevention of cervical adhesion after LEEP. Key words: Cervix uteri; Cervical intraepithelial neoplasia; Loop electrosurgical excision procedure; Cervical adhesion; Program evaluation