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Competing Interests: Competing interests: EAJ Advisory board fees by MSD and Roche, grants by MSD through institution.MA was supported by the Horizon 2020 Framework Programme for Research and Innovation of the European Commission, through the RISCC Network (grant no. 847845); the VALCOR project (VALidation of SARS-CORona Virus-2 assays). MG declares having received travel support and honororia from MSD to be a speaker.

Background: A significant number of women are diagnosed with minor cytological abnormalities on cervical screening. Many authorities recommend surveillance as spontaneous regression might occur. However, attendance for cytological follow-up decreases with time and might put some women at risk of developing invasive disease., Objectives: To assess the optimum management strategy for women with minor cervical cytological abnormalities (atypical squamous cells of undetermined significance - ASCUS or low-grade squamous intra-epithelial lesions - LSIL) at primary screening in the absence of HPV (human papillomavirus) DNA test., Search Methods: We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL Issue 4, 2016), MEDLINE (1946 to April week 2 2016) and Embase (1980 to 2016 week 16)., Selection Criteria: We included randomised controlled trials (RCTs) comparing immediate colposcopy to cytological surveillance in women with atypical squamous cells of undetermined significance (ASCUS/borderline) or low-grade squamous intra-epithelial lesions (LSIL/mild dyskaryosis)., Data Collection and Analysis: The primary outcome measure studied was the occurrence of cervical intra-epithelial neoplasia (CIN). The secondary outcome measures studied included default rate, clinically significant anxiety and depression, and other self-reported adverse effects.We classified studies according to period of surveillance, at 6, 12, 24 or 36 months, as well as at 18 months, excluding a possible exit-examination. We calculated pooled risk ratios (RR) and 95% confidence intervals (CI) using a random-effects model with inverse variance weighting. Inter-study heterogeneity was assessed with I 2 statistics., Main Results: We identified five RCTs with 11,466 participants that fulfilled the inclusion criteria. There were 18 cases of invasive cervical cancer, seven in the immediate colposcopy and 11 in the cytological surveillance groups, respectively. Although immediate colposcopy detects CIN2+ and CIN3+ earlier than cytology, the differences were no longer observed at 24 months (CIN2+: 3 studies, 4331 women; 17.9% versus 18.3%, RR 1.14, CI 0.66 to 1.97; CIN3+: 3 studies, 4331 women; 10.3% versus 11.9%, RR 1.02, CI 0.53 to 1.97). The inter-study heterogeneity was considerable (I 2 greater than 90%). Furthermore, the inclusion of the results of the exit examinations at 24 months, which could inflate the CIN detection rate of cytological surveillance, may have led to study design-derived bias; we therefore considered the evidence to be of low quality.When we excluded the exit examination, the detection rate of high-grade lesions at the 18-month follow-up was higher after immediate colposcopy (CIN2+: 2 studies, 4028 women; 14.3% versus 10.1%, RR 1.50, CI 1.12 to 2.01; CIN3+: 2 studies, 4028 women, 7.8% versus 6.9%, RR 1.24, CI 0.77 to 1.98) both had substantial inter-study heterogeneity (I 2 greater than 60%) and we considered the evidence to be of moderate quality).The meta-analysis revealed that immediate referral to colposcopy significantly increased the detection of clinically insignificant cervical abnormalities, as opposed to repeat cytology after 24 months of surveillance (occurrence of koilocytosis: 2 studies, 656 women; 32% versus 21%, RR 1.49, 95% CI 1.17 to 1.90; moderate-quality evidence) incidence of any CIN: 2 studies, 656 women; 64% versus 32%, RR 2.02, 95% CI 1.33 to 3.08, low-quality evidence; incidence of CIN1: 2 studies, 656 women; 21% versus 8%, RR 2.58, 95% CI 1.69 to 3.94, moderate-quality evidence).Due to differences in trial designs and settings, there was large variation in default rates between the included studies. The risk for default was higher for the repeat cytology group, with a four-fold increase at 6 months, a six-fold at 12 and a 19-fold at 24 months (6 months: 3 studies, 5117 women; 6.3% versus 13.3%, RR 3.85, 95% CI 1.27 to 11.63, moderate-quality evidence; 12 months: 3 studies, 5115 women; 6.3% versus 14.8%, RR 6.39, 95% CI 1.49 to 29.29, moderate-quality evidence; 24 months: 3 studies, 4331 women; 0.9% versus 16.1%, RR 19.1, 95% CI 9.02 to 40.43, moderate-quality evidence)., Authors' Conclusions: Based on low- or moderate-quality evidence using the GRADE approach and generally low risk of bias, the detection rate of CIN2+ or CIN3+ after two years does not appear to differ between immediate colposcopy and cytological surveillance in the absence of HPV testing, although women may default from follow-up. Immediate colposcopy probably leads to earlier detection of high-grade lesions, but also detects more clinically insignificant low-grade lesions. Colposcopy may therefore be the first choice when good compliance is not assured. These results emphasize the need for an accurate reflex HPV triage test to distinguish women who need diagnostic follow-up from those who can return safely to routine recall.

We performed a systematic review and meta-analysis to explore the optimum management strategy for women with atypical squamous cells of undetermined significance (ASCUS/borderline) or low-grade squamous intra-epithelial lesions (LSIL/mild dyskaryosis) cytological abnormalities at primary screening in the absence of HPV DNA test. We searched MEDLINE, EMBASE and CENTRAL and included randomised controlled trials comparing immediate colposcopy to cytological surveillance in women with ASCUS/LSIL. The outcomes of interest were occurrence of different histological grades of cervical intraepithelial neoplasia (CIN) and default rates during follow-up. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effect model and with inverse variance weighting. Interstudy heterogeneity was assessed using I 2 statistics. Six RCTs were included. Immediate colposcopy significantly increased detection of unimportant abnormalities as opposed to repeat cytology (koilocytosis: 32 vs. 21%, RR: 1.49, 95% CI = 1.17-1.90); CIN1: 21 vs. 8%, RR: 2.58, 95% CI = 1.69-3.94). Although immediate colposcopy detected CIN2, CIN2+, and CIN3+ earlier than cytology, the differences were no longer observed at 24 months (CIN3+: 10.3 vs.11.9%, RR: 1.02, 95% CI = 0.53-1.97), with significant interstudy heterogeneity (p < 0.001, I 2  = 93%). Default risk was significantly higher for repeat cytology (6 months: 6.3 vs. 13.3%, RR: 3.85, 95% CI = 1.27-11.63; 12 months: 6.3 vs. 14.8%, RR: 6.39, 95% CI = 1.24-32.95; 24 months: 0.9 vs. 16.1%, RR: 19.1, 95% CI = 9.02-40.4). Detection of CIN2+ for cytological surveillance over two years is similar to that of immediate colposcopy, although patients may default. Colposcopy may be first choice when good compliance is not assured, but may increase detection of insignificant lesions. This emphasizes the need for a reflex triage test to distinguish women who need diagnostic work-up from those who can return to routine recall., (© 2016 UICC.)

Objective: To assess the level of compliance with follow-up over time after treatment for preinvasive and Stage Ia1 lesions of the cervix. To compare the average interval between visits with the interval prescribed by protocol and to evaluate the use of this difference as a measure of compliance., Design: Retrospective observational study. Setting. London university hospital., Population: Women who received treatment for preinvasive (CINI-III, AIS) or Stage Ia1 cervical lesions., Methods: Attendance data were obtained from hospital-based colposcopy and community-based databases., Main Outcome Measures: The average interval between the appointments attended by each woman was compared with the planned interval between visits. The time that elapsed since the previous appointment attended was calculated for each visit and correlated with the time since treatment., Results: 1013 women attended 4128 follow-up visits in the colposcopy clinic and in the community. Twenty-two (2.2%) women never attended any post-treatment appointment and 209 (21.0%) of the 991 women who attended at least once, did so on average more than 12 months later than specified by the follow-up protocol. There was a highly significant correlation between the interval since the previous appointment and the time since treatment (Kendall's tau b = 0.529614, two-sided p < 0.0001), showing that compliance deteriorates with increasing time since treatment., Conclusions: Comparing the average interval between attendances with the planned interval prescribed by protocol is a sensitive measure of compliance. Compliance with follow-up deteriorates significantly with time since treatment. This decline in compliance may contribute to the increased risk of invasive disease after treatment., (© 2012 The Authors  Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective of this study is to investigate the potential of the learning vector quantizer neural network (LVQ-NN) classifier on various diagnostic variables used in the modern cytopathology laboratory and to build an algorithm that may facilitate the classification of individual cases. From all women included in the study, a liquid-based cytology sample was obtained; this was tested via HPV DNA test, E6/E7 HPV mRNA test, and p16 immunostaining. The data were classified by the LVQ-NN into two groups: CIN-2 or worse and CIN-1 or less. Half of the cases were used to train the LVQ-NN; the remaining cases (test set) were used for validation. Out of the 1258 cases, cytology identified correctly 72.90% of the CIN-2 or worst cases and 97.37% of the CIN-1 or less cases, with overall accuracy 94.36%. The application of the LVQ-NN on the test set allowed correct classification for 84.62% of the cases with CIN-2 or worse and 97.64% of the cases with CIN-1 or less, with overall accuracy of 96.03%. The use of the LVQ-NN with cytology and the proposed biomarkers improves significantly the correct classification of cervical precancerous lesions and/or cancer and may facilitate diagnosis and patient management.

This overview presents the up-to-date evidence on colposcopy practice and other diagnostic modalities such as HPV DNA test and cytology for cervical intraepithelial neoplasia (CIN). Current evidence supports the use of colposcopy for the detection of intraepithelial lesions as a second line tool. CIN treatment involves either excisional or destructive techniques, usually performed under local anesthesia. Although a debate exists about the most efficient approach, the currently available evidence reveals no differences in efficacy among the available conservative methods of treatment. New evidence supports treatment by destructive rather than excisional techniques, at least for low grade lesions in women wishing future childbearing, as they appear to have no apparent pregnancy-related morbidity. Treatment failures rates might increase in cases of involved excision margins, older age or glandular involvement. There is no worldwide consensus on the optimal follow-up policy, interventions or frequency in surveillance after treatment. HPV DNA test combined with either colposcopy or cytology is a promising combination for the early detection of treatment failures due to residual disease. Existing guidelines should probably be updated incorporating the new information emerged from recently published work.

Purpose: To establish whether information leaflets and appointment reminders improve attendance for diagnostic colposcopy., Design & Setting: Randomised controlled trial in an inner city colposcopy clinic., Participants: 500 women newly referred to the colposcopy clinic with abnormal cervical screening smear results were randomly assigned to an intervention or control group using computer-generated numbers., Intervention: 233 women referred for colpoposcopy were sent a comprehensive information leaflet with their appointment details and additionally were sent reminder letters regarding their appointment 7-10 days prior to their appointment date., Control: 267 women were sent the standard basic information prior to their appointment., Main Outcome Measure: Attendance and default rates for diagnostic colposcopy., Results: Default in the intervention arm was 42 out of 233 (18%) compared with 93 out of 267 (35%) in the control arm., Conclusion: Improved communication and information in the form of a detailed leaflet and a reminder letter for women with a recently abnormal smear result increased attendance for initial colposcopy assessment.

Please cite this paper as: Phadnis S, Atilade A, Bowring J, Kyrgiou M, Young M, Evans H, Paraskevaidis E, Walker P. Regeneration of cervix after excisional treatment for cervical intraepithelial neoplasia: a study of collagen distribution. BJOG 2011;118:1585-1591. Objective To study the distribution of collagen in the regenerated cervical tissue after excisional treatment for cervical intraepithelial neoplasia (CIN). Design Cohort study. Setting A large tertiary teaching hospital in London. Population Women who underwent repeat excisional treatment for treatment failure or persistent CIN. Methods Eligible women who underwent a repeat excisional treatment for treatment failure, including hysterectomy, between January 2002 and December 2007 in our colposcopy unit were identified by the Infoflex® database and SNOMED encoded histopathology database. Collagen expression was assessed using picro-Sirius red stain and the intensity of staining was compared in paired specimens from the first and second treatments. Main outcome measure Differences in collagen expression were examined in the paired excisional treatment specimens. Results A total of 17 women were included. Increased collagen expression in the regenerated cervical tissue of the second cone compared with the first cone was noted in six women, decreased expression was noted in five women, and the pattern of collagen distribution was equivocal in six women. Conclusion There is no overall change in collagen distribution during regeneration following excisional treatment for CIN. [ABSTRACT FROM AUTHOR]

Cytology remains the mainstay for cervical screening. The need to achieve effective management, limit complications, and preserve reproductive function led to the popularity of local treatment. Although the cure rates for ablative and excisional methods are similar, the excisional method provides a more reliable histopathological diagnosis. Recent evidence revealed increased perinatal morbidity after treatment that appears to be related to the proportion of cervix removed. The human papillomavirus (HPV) DNA test appears to enhance the detection of disease in primary screening, in the triage of minor cytological abnormalities, and in follow-up. Further research on the clinical application of a scoring system is ongoing. The vaccines are now available and appear to be safe, well tolerated, and highly efficacious in HPV naive women. A synergy of vaccination and screening will be required. Treatment for early cervical cancer is increasingly shifting toward more fertility-sparing surgical techniques. Careful selection of patients is essential. [ABSTRACT FROM AUTHOR]

Summary: Background: A significant number of women are diagnosed with a low grade cytological abnormality on cervical screening. Many authorities recommend surveillance as spontaneous regression might occur. However, protracted attendance for cytological follow-up decreases with time and might put some women at risk of developing invasive disease. The aim of this review was to assess management options for women with minor cervical disease. Methods: An electronic literature search was conducted. All randomised controlled studies comparing immediate colposcopy to cytological surveillance in women with cervical atypia/borderline nuclear changes or low-grade lesions were included. The main outcomes studied were the default rates from the colposcopy clinic and the histological status of biopsies within immediate management protocols compared to biopsies taken on completion of surveillance. Pooled relative risks and 95% confidence intervals were calculated using a random-effect model and inter-study heterogeneity was assessed with Cochrane’s Q-test. Results: Three randomised controlled trials identified from the literature search with different surveillance periods were combined. The analysis revealed that compliance with follow-up declines over time and reaches significance at the end of 24 months of surveillance (RR: 74.10 [10.36, 529.79]). There was a significantly higher incidence of HPV and CIN 1 in those women referred to immediate colposcopy/treatment compared to those at the end of 24 months surveillance period (32% vs 21%) (RR 1.49, 95% CI 1.17–1.90) and (21% vs 8%) (RR 2.58, 95% CI 1.69–3.94), respectively, possibly explained by spontaneous regression of clinically non-important lesions. Finally, there was no significant difference in the incidence of CIN2 or worse at initial colposcopy compared with the observation group (24 months) (RR 1.72, 95% CI 0.85–3.48). Conclusion: Cytological surveillance puts women at risk as many show poor compliance and such women might have occult high grade abnormalities. A general policy should be immediate colposcopy for all women after a single low grade cervical smear. [Copyright &y& Elsevier]

A response by E. Paraskevaidis and colleagues to a letter to the editor about their article on the psychological problems experienced by women undergoing colposcopy is presented.

The article focuses on colposcopy and the author reflects whether gynecologists stopped considering ablative treatment prematurely. A meta-analysis by Kyrgiou and others confirms that excisional treatments for cervical cancer could adversely affect future pregnancy results. The author discusses the recommended UK practice and the European Guidelines, which support ablative treatment for young women with low-grade disease and satisfactory colposcopy.

Following the publication of the European consensus statement on standards for essential colposcopy in 2020, the need for standards relating to more complex and challenging colposcopy practice was recognised. These standards relate to colposcopy undertaken in patients identified through cervical screening and tertiary referrals from colposcopists who undertake standard colposcopy only. This set of recommendations provides a review of the current literature and agreement on care for recognised complex cases. With good uptake of human papillomavirus (HPV) immunisation, we anticipate a marked reduction in cervical disease over the next decade. Still, the expert colposcopist will continue to be vital in managing complex cases, including previous cervical intraepithelial neoplasia (CIN)/complex screening histories and multi-zonal disease. To provide expert guidance on complex colposcopy cases through published evidence and expert consensus. Members of the EFC and ESGO formed a working group to identify topics considered to be the remit of the expert rather than the standard colposcopy service. These were presented at the EFC satellite meeting, Helsinki 2021, for broader discussion and finalisation of the topics. The agreed standards included colposcopy in pregnancy and post-menopause, investigation and management of glandular abnormalities, persistent high-risk HPV+ with normal/low-grade cytology, colposcopy management of type 3 transformation zones (TZ), high-grade cytology and normal colposcopy, colposcopy adjuncts, follow-up after treatment with CIN next to TZ margins and follow-up after treatment with CIN with persistent HPV+, and more. These standards are under review to create a final paper of consensus standards for dissemination to all EFC and ESGO members. [ABSTRACT FROM AUTHOR]