European consensus statement on expert colposcopy.

BACKGROUND: 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. AIMS: To provide expert guidance on complex colposcopy cases through published evidence and expert consensus. MATERIAL & METHODS: 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. RESULTS & DISCUSSION: 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.

European consensus statement on essential colposcopy.

This European consensus statement on essential colposcopy provides standards for the general colposcopist seeing women referred for colposcopy with an abnormal cervical screening test (including cytology and HPV tests) or with a clinically suspicious cervix. The article gives guidance regarding the aims and conduct of colposcopy. Recommendations are provided on colposcopy technique, the management of common colposcopy issues, treatment and follow-up of after treatment of CIN or early stage cervical. Colposcopists should make an informed decision on the management of each individual that is referred and organize appropriate follow-up. Cervical cancer is still a major health issue and the quality of care can only improve if there is a structured guidance for women with an abnormal smear or suspicious cervix.

Reduction in colposcopy workload and associated clinical activity following human papillomavirus (HPV) catch-up vaccination programme in Scotland: an ecological study.

OBJECTIVE: To measure patterns of clinical activity at colposcopy before and after vaccinated women entered the Scottish Cervical Screening Programme (SCSP). DESIGN: Population-based observational study using nationally collected data. SETTING: Scottish colposcopy clinics. SAMPLE: All women with a date of birth on or after 1 January 1985 who attended colposcopy in Scotland between 2008 and 2014. METHODS: Routinely collected data from the Scottish National Colposcopy Clinical Information Audit System (NCCIAS) were extracted, including: referral criteria, referral cervical cytology, colposcopic findings, clinical procedures, and histology results. Analysis was restricted to those referred to colposcopy at age 20 or 21 years. MAIN OUTCOME MEASURES: Referral criteria, positive predictive value of colposcopy, default rates, and rates of cervical biopsies and treatments. RESULTS: A total of 7372 women referred for colposcopy at age 20 or 21 years were identified. There was a downward trend in the proportion of those referred with abnormal cytology (2008/9, 91.0%; 2013/14, 90.3%; linear trend P = 0.03). Women were less likely to have diagnostic or therapeutic interventions. The proportion with no biopsy (2008/9, 19.5%; 2013/14, 26.9%; linear trend P < 0.0001) and no treatment (2008/9, 74.9%; 2013/14, 91.8%; linear trend P < 0.0001) increased over the period of observation. CONCLUSIONS: A reduction in clinical activity related to abnormal screening referrals is likely to be associated with the human papillomavirus (HPV) catch-up immunisation programme. Referral criteria and the service provision of colposcopy needs to be planned carefully, taking account of the increasing number of women who have been immunised against HPV that will be entering cervical screening programmes worldwide. TWEETABLE ABSTRACT: Colposcopy referral criteria and service planning need attention following HPV immunisation programme.

The impact of human papillomavirus type on colposcopy performance in women offered HPV immunisation in a catch-up vaccine programme: a two-centre observational study.

OBJECTIVE: To determine whether human papillomavirus (HPV) immunisation has affected the prevalence of HPV genotypes and colposcopic features of cervical intraepithelial neoplasia (CIN) in young women referred for colposcopy. DESIGN: A two-centre observational study including vaccinated and unvaccinated women. SETTING: Colposcopy clinics serving two health regions in Scotland, UK. POPULATION: A total of 361 women aged 20-25 years attending colposcopy following an abnormal cervical cytology result at routine cervical screening. METHODS: Cervical samples were obtained from women for HPV DNA genotyping and mRNA E6/E7 expression of HPV 16, 18, 31, 33, and 45. Demographic data, cytology, and histology results and colposcopic features were recorded. Chi-square analysis was conducted to identify associations between vaccine status, HPV genotypes, and colposcopic features. MAIN OUTCOME MEASURES: Colposcopic features, HPV genotypes, mRNA expression, and cervical histology. RESULTS: The prevalence of HPV 16 was significantly lower in the vaccinated group (8.6%) compared with the unvaccinated group (46.7%) (P = 0.001). The number of cases of CIN2+ was significantly lower in women who had been vaccinated (P = 0.006). The HPV vaccine did not have a statistically significant effect on commonly recognised colposcopic features, but there was a slight reduction in the positive predictive value (PPV) of colposcopy for CIN2+, from 74% (unvaccinated) to 66.7% (vaccinated). CONCLUSIONS: In this group of young women with abnormal cytology referred to colposcopy, HPV vaccination via a catch-up programme reduced the prevalence of CIN2+ and HPV 16 infection. The reduced PPV of colposcopy for the detection of CIN2+ in women who have been vaccinated is at the lower acceptable level of the UK national cervical screening programme guidelines. TWEETABLE ABSTRACT: Reduction of hrHPV positivity and CIN in immunised women consistent with lower PPV of colposcopy for CIN2+.

Psychosocial morbidity in women with abnormal cervical cytology managed by cytological surveillance or initial colposcopy: longitudinal analysis from the TOMBOLA randomised trial.

OBJECTIVE: To compare psychosocial outcomes (follow-up related worries and satisfaction with follow-up related information and support) over 30 months of two alternative management policies for women with low-grade abnormal cervical cytology. METHODS: Women aged 20-59 years with low-grade cytological abnormalities detected in the National Health Service Cervical Screening Programme were randomised to cytological surveillance or initial colposcopy. A total of 3399 women who completed psychosocial questionnaires at recruitment were invited to complete questionnaires at 12, 18, 24 and 30 months. Linear mixed models were used to investigate differences between arms in the two psychosocial outcomes. Each outcome had a maximum score of 100, and higher scores represented higher psychosocial morbidity. RESULTS: On average, over 30 months, women randomised to colposcopy scored 2.5 points (95%CI -3.6 to -1.3) lower for follow-up related worries than women randomised to cytological surveillance. Women in the colposcopy arm also scored significantly lower for follow-up related satisfaction with information and support (-2.4; -3.3 to -1.4) over 30 months. For both outcomes, the average difference between arms was greatest at 12th- and 18th-month time points. These differences remained when the analysis was stratified by post-school education. CONCLUSIONS: Women with low-grade cytology, irrespective of their management, have substantial initial psychosocial morbidity that reduces over time. Implementation of newer screening strategies, which include surveillance, such as primary HPV screening, need to consider the information and support provided to women. © 2016 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.

A normal colposcopy examination fails to provide psychological reassurance for women who have had low-grade abnormal cervical cytology.

OBJECTIVE: Worldwide, each year, large numbers of women are referred for colposcopy following low-grade abnormal cervical cytology. Many have no visible abnormality on examination. The risk of cervical intra-epithelial neoplasia grade 2/3 (CIN2/3) in these women is low. It is unknown whether, for women, a normal colposcopy resolves the anxiety which often follows the receipt of an abnormal cytology result. We investigated the prevalence of adverse psychological outcomes over 30 months following a normal colposcopy. METHODS: This cohort study was nested within the UK TOMBOLA randomized controlled trial. Women aged 20-59 years, with recent low-grade cytology, who had a satisfactory colposcopy examination and normal transformation zone, completed the Hospital Anxiety and Depression Scale (HADS) and Process Outcome Specific Measure (POSM) at recruitment and during follow-up (12, 18, 24 and 30 months post-recruitment). Outcomes included percentages reporting significant anxiety (HADS anxiety subscale score ≥11), significant depression (HADS depression subscale score ≥8) or worries about the result of the next cytology test, cervical cancer, having sex, future fertility and general health at each time point (point prevalence) and during follow-up (cumulative prevalence). RESULTS: The study included 727 women. All psychological measures (except depression) had high prevalence at recruitment, falling substantially by 12 months. During follow-up, the cumulative prevalence of significant anxiety was 27% and significant depression was 21%. The most frequently reported worry was that the next cytology test would be abnormal (cumulative prevalence of 71%; point prevalence of ≥50% at 12 and 18 months). The cumulative prevalence values of worries about cervical cancer, having sex and future fertility were 33%, 20% and 16%, respectively. CONCLUSIONS: For some women who have low-grade cytology, a normal colposcopy does not appear to provide psychological reassurance.

Management of women with low grade cytology: how reassuring is a normal colposcopy examination?

OBJECTIVES: To determine the rate of cervical intraepithelial neoplasia grade 2 (CIN2+) in women with low grade cervical cytology and a normal colposcopy examination over 3 years of follow-up. DESIGN: Cohort study within a randomised controlled trial. SETTING: NHS Cervical Screening Programmes in Grampian, Tayside and Nottingham. POPULATION: Eight hundred and eighty-four women aged 20-59 years with borderline nuclear abnormalities (BNA) or mild dyskaryosis with a normal and adequate colposcopy examination. METHODS: Samples at baseline were tested for 14 high-risk (Hr) types using GP5+6+ methodology and for HPV 16 and 18 using type-specific primers. Women were followed up post-colposcopy by cervical cytology at 6-month intervals in primary care. After 3 years, women were invited for an exit colposcopy examination and underwent LLETZ if any colposcopic abnormality was identified. MAIN OUTCOME MEASURES: Absolute and relative risks of CIN2+ during follow-up and/or at exit colposcopy. RESULTS: The median age was 36 years. The absolute risk of developing CIN2+ within 3 years was 1.86 per 100 woman years and for CIN3+, 0.64 per 100 woman years. One microinvasive cancer was identified. The relative risk (RR) was highest for women with initial mild dyskaryosis who were HrHPV-positive (RR 5.86, 95% confidence interval 2.53-13.56) compared with women with BNA who were HrHPV-negative. CONCLUSION: For women with low grade cervical cytology, the risk of a high grade CIN within 3 years of a normal colposcopy examination is low. Women can be reassured that, even with a positive HPV test, the risk of developing CIN2 or worse is sufficiently low to return to the routine 3-year recall.

Is there an increase in the incidence of uterine carcinosarcoma in north-east Scotland? A 19 years population-based cohort study.

BACKGROUND AND AIMS: The incidence of uterine carcinosarcoma and factors associated with its survival are little known and this study helps to address this question for women residing in north-east Scotland. METHODS AND RESULTS: Data were collected from women diagnosed with carcinosarcoma of the uterus residing in north-east of Scotland from 1991 to 2009. Kaplan-Meier plots and Cox regression analysis were used for analysis. A total of 43 women were analysed during this period. The median survival was 25 months. The estimated five-year survival for stage I/II disease was 52.5% (95% CI: 30.5-74.5%). The 2-year survival rate for stage III/IV disease was 46% (95% CI: 16-75%). There was an increase in the incidence during this period. Improved survival was seen in early-stage disease (FIGO stages I and II) and in the absence of lymphovascular space invasion (LVSI; p = 0.015). A total of 26% of the women had a history of tamoxifen usage with no effect seen on survival. Multivariate analysis showed that when treatment modality and LVSI were adjusted for FIGO staging, there was no statistical significance in the survival outcomes. CONCLUSION: The incidence of uterine carcinosarcomas is increasing parallel with endometrial carcinomas with no significant effect of tamoxifen on survival.

The development and evaluation of a questionnaire to assess the impact of vulval intraepithelial neoplasia: a questionnaire study.

OBJECTIVE: To develop and evaluate a questionnaire to assess the burden of vulval intraepithelial neoplasia (VIN) in women. DESIGN: A questionnaire development study. SETTING: Vulval Disorders Clinic serving a regional population. SAMPLE: Fifty-eight women with a histological diagnosis of VIN registered with the Vulval Disorders Clinic. METHODS: A 37-item questionnaire was developed through a comprehensive literature review, consultation with specialist clinicians and pretesting to assess the burden experienced by women. The questionnaire was assessed for validity and reliability against existing questionnaires used in related disease areas. MAIN OUTCOME MEASURES: Spearman correlations were calculated between items in the VIN questionnaire with the scores of the Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), Sabbatsberg Sexual Self-Rating Scale (SSRS) and the Process Outcome Specific Measure (POSM) to assess the new questionnaire's validity. Internal consistency was measured using Cronbach's alpha. Test-retest reliability was calculated using quadratic weighted kappa. RESULTS: The VIN questionnaire had a high degree of internal consistency (Cronbach's alpha, 0.89). Test-retest reliability was assessed, with most questions showing a quadratic weighted kappa value of 0.5 or above. Most questions showed a stronger correlation with the corrected total VIN score than with HADS anxiety and depression subscales and the SSRS, indicating discriminant validity. Most questions correlated significantly with the DLQI and POSM scores, indicating convergent validity. CONCLUSIONS: Initial assessment of the VIN questionnaire demonstrated that it is a valid and reliable measure of the burden of disease for women. The questionnaire could be used to compare new and existing treatments for VIN or to assess or monitor the impact of care.

Real-life experience of managing vulval erosive lichen planus: a case-based review and U.K. multicentre case note audit.

BACKGROUND: There is a lack of published evidence for treatment and outcome measures for vulval erosive lichen planus (ELPV). OBJECTIVES: To conduct a multicentre case note review to examine real-life management of ELPV comparing current U.K. practice against an agreed audit standard. METHODS: Criteria for standards of care for which to evaluate current service provision were set following communication with experts from the British Society for the Study of Vulval Disease. Participants from 10 U.K. centres included nine dermatologists and one gynaecologist who run specialist vulval clinics. Standards examined the documentation of disease severity/impact measures, the use of diagnostic biopsies, treatments used and assessment of treatment response. RESULTS: Audit data were collected from 172 patients. Documentation of symptoms/clinical findings was excellent (99%, 170/172). A schematic diagram was present in the notes of 87% (150/172). Patient-related disease impact measures including Dermatology Life Quality Index (3%, 6/172) or visual analogue scales (1%, 2/172) were less well documented. Biopsies were performed in 78% (135/172); 71% (96/135) showed histological features consistent with erosive lichen planus. Squamous cell carcinoma developed in four patients (two vulval, two oral) and vulval intraepithelial neoplasia in two further patients. Recommended first-line treatment with a very potent topical steroid was used in 75% (129/172) with improvement in 66% (85/129). Significant variation in second-line therapy was seen. CONCLUSIONS: Wide variation in U.K. practice demonstrates the absence of standardized guidance for treating ELPV and the need for vulval-specific outcomes. This audit should act as a framework towards improving ELPV management and to plan future research in this area.

A population-based case-control study of aetiological factors associated with vulval lichen sclerosus.

We aimed to investigate the association between possible aetiological factors and the risk of developing vulval lichen sclerosus (VLS). A population-based case-control questionnaire study was performed comparing women with a diagnosis of VLS (n= 92), with those attending a general gynaecology clinic with no known anogenital dermatosis (n= 66). After adjustment for confounders, factors associated with VLS included a family history of diabetes mellitus (OR= 7.0, p= 0.012) and previous pelvic surgery (OR= 4.75, p= 0.007). The use of barrier and progesterone only methods of contraception (OR= 0.19, p= 0.045), hormone replacement therapy (OR= 0.209, p= 0.025) or hayfever (OR= 0.18, p= 0.008) appeared to be associated with a reduced risk of VLS. In conclusion, we were unable to confirm many proposed aetiological theories associated with the development of VLS, in particular those associated with autoimmunity.

The prospective management of women with newly diagnosed vulval intraepithelial neoplasia: clinical outcome and quality of life.

Vulval intraepithelial neoplasia (VIN) is a premalignant skin condition with significant morbidities from standard surgical treatment. This two-year prospective study recruited women with newly diagnosed VIN for careful observation rather than primary surgical excision. Surgery was performed to exclude progression or for uncontrollable symptoms. Participants were seen six-monthly for clinical review and completion of questionnaires assessing depression and anxiety, quality of life, sexual functioning, and partner relationships. Eight women were recruited. Six women required immediate treatment and two women were observed carefully. By study completion, seven participants had undergone surgical treatment, often for symptom control. Women scored poorly on quality of life and sexual functioning scores; this did not appear to be due to depression or anxiety. In conclusion, careful observation does not appear a feasible option for most women with VIN since the majority require surgical treatment. VIN has an adverse impact on quality of life and sexual functioning.

HPV testing as an adjunct to cytology in the follow up of women treated for cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate human papillomavirus (HPV) testing in combination with cytology in the follow up of treated women. DESIGN: A prospective study. SETTING: Three UK centres: Manchester, Aberdeen and London. POPULATION OR SAMPLE: Women treated for cervical intraepithelial neoplasia (CIN). METHODS: Women were recruited at 6 months of follow up, and cytology and HPV testing was carried out at 6 and 12 months. If either or both results were positive, colposcopy and if appropriate, a biopsy and retreatment was performed. At 24 months, cytology alone was performed. MAIN OUTCOME MEASURES: Cytology and histology at 6, 12 and 24 months. RESULTS: Nine hundred and seventeen women were recruited at 6 months of follow up, with 778 (85%) and 707 (77.1%) being recruited at 12 and 24 months, respectively. At recruitment, 700 women had had high-grade CIN (grades 2 or 3) and 217 had CIN1. At 6 months, 14.6% were HPV positive and 10.7% had non-negative cytology. Of those with negative cytology, 9% were HPV positive. Of the 744 women who were cytology negative/HPV negative at baseline, 3 women with CIN2, 1 with CIN3, 1 with cancer and 1 with vaginal intraepithelial neoplasia (VAIN)1 were identified at 24 months. Nine of 10 cases of CIN3/cervical glandular intraepithelial neoplasia (CGIN) occurred in HPV-positive women. At 23 months, cancer was identified in a woman treated for CGIN with clear resection margins, who had been cytology negative/HPV negative at both 6 and 12 months. CONCLUSIONS: Women who are cytology negative and HPV negative at 6 months after treatment for CIN can safely be returned to 3-year recall.

The impact of microinvasive cancer of the cervix on women during follow-up.

The psychologic and psychosexual sequelae of cervical screening and disease are well recognized but most research has focused on women with cervical intraepithelial neoplasia (CIN) or women with early (stage IB) to advanced cervical cancer. There has been little work looking at women with microinvasive cancer as a unique clinical identity. Many of these women have a similar diagnostic, treatment, and follow-up pathway to those with high-grade CIN. This could result in unrecognized and ongoing health concerns. We report on a questionnaire-based case-control study, comparing the concerns of women with microinvasive cervical cancer with those of women with high-grade CIN. Women with microinvasive cancer and controls with CIN2/3 diagnosed between 2000 and 2006, from a geographically defined population, were recruited and invited to complete a postal questionnaire consisting of the Hospital Anxiety and Depression Scale (HADS) and the Process Outcome Specific Measure (POSM). Twenty-eight women diagnosed with microinvasive cancer were identified and 18 participated (response rate 64%). Fifty-eight controls were matched by age and year of treatment with 26 responding (45%). About 18% of women with microinvasive cancer had a HADS depression score of 8 or more, compared to 12% of those with CIN (P = not significant). The HADS anxiety score of 8 or more occurred in 35% of each group. There were no significant differences in terms of POSM results for sexual activity, fertility, and developing cervical cancer in the future between cases and controls. We did not find a difference between women with a previous diagnosis of microinvasive cancer and those with high-grade CIN, in terms of ongoing concerns during their follow-up. We did not identify any additional concerns for women with microinvasive cancer in the care provided in the colposcopy service.

Lifestyle and socio-demographic factors associated with high-risk HPV infection in UK women.

The world age-standardised prevalence of high-risk HPV (hrHPV) infection among 5038 UK women aged 20-59 years, with a low-grade smear during 1999-2002, assessed for eligibility for TOMBOLA (Trial Of Management of Borderline and Other Low-grade Abnormal smears) was 34.2%. High-risk HPV prevalence decreased with increasing age, from 61% at ages 20-24 years to 14-15% in those over 50 years. The age-standardised prevalence was 15.1, 30.7 and 52.7%, respectively, in women with a current normal, borderline nuclear abnormalities (BNA) and mild smear. In overall multivariate analyses, tertiary education, previous pregnancy and childbirth were associated with reduced hrHPV infection risk. Risk of infection was increased in non-white women, women not married/cohabiting, hormonal contraceptives users and current smokers. In stratified analyses, current smear status and age remained associated with hrHPV infection. Data of this type are relevant to the debate on human papillomavirus (HPV) testing in screening and development of HPV vaccination programmes.

An audit of the quality of endometrial cancer care in a specialised unit.

BACKGROUND: Endometrial cancer is the 5th most common female cancer in Scotland and though cure rates are good, 25% of women still die of their disease. Staging has been shown to be poorly performed in Scotland-wide audit and inadequate staging is a predictor of worse outcome. Only 12% of women with endometrial cancer in Scotland are operated upon by a specialist gynaecological oncologist. AIMS: To determine if the quality of staging information in endometrial cancer is improved in a region where all cases are managed by specialist gynaecological oncologists. METHODS: All 108 women diagnosed and treated with endometrial cancer in Grampian in 2002 and 2003 had a retrospective case note assessment of the completeness of staging information. This was compared to previously published Scottish results. RESULTS: Completeness of staging was high. The International Federation of Gynecology and Obstetrics (FIGO) stage was available in 100% of women. Chest X Ray was performed in 85% and peritoneal cytology in 93%. Pelvic lymphadenectomy was performed in 28%. All these results were significantly better than in the Scottish audit. CONCLUSION: Centralisation of women with endometrial cancer results in accurate staging information. However it is not yet known what effect this may have on outcome.

Human papillomavirus 16 infection in adenocarcinoma of the cervix.

The impact of the success of organised cervical screening programme results in a steady decline of the incidence of squamous cell carcinoma of the cervix but a concomitant increase in the incidence of the less common histological subtypes, particularly adenocarcinoma of the cervix (ACC). Although Human papillomavirus (HPV) infection is believed to be a necessary cause of cervical cancer, its role in the pathogenesis of ACC is not well established. Established associations between oncogenic strains of HPV and ACC are based on molecular studies carried out on entire tumour block sections. In this study, the cervical adenocarcinoma cells of a 10-year cohort of women diagnosed with ACC were dissected using the PixCell II Laser Microdissecting System to detect the HPV 16 genome sequence using the real-time quantitative polymerase chain reaction to confirm the presence of HPV DNA within ACC cells. By coupling these two sophisticated techniques, the HPV DNA copy number cell could be calculated to investigate its role. The prevalence of HPV 16 infection in this cohort was 24%, which is significantly higher than the control group (chi(2), P=0.014). Women with ACC also had significantly higher HPV DNA copy number per cell compared to the control group (P=0.00007). Higher HPV DNA copy number is associated with risk of developing ACC.