The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) consensus statement on the management of vaginal intraepithelial neoplasia.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vaginal intraepithelial neoplasia (VaIN). The management of VaIN varies according to the grade of the lesion: VaIN 1 (low grade vaginal squamous intraepithelial lesions (SIL)) can be subjected to follow-up, while VaIN 2-3 (high-grade vaginal SIL) should be treated. Treatment needs individualization according to the patient's characteristics, disease extension and previous therapeutic procedures. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Total vaginectomy is used only in highly selected cases of extensive and persistent disease. Carbon dioxide (CO2) laser may be used as both an ablation method and an excisional one. Reported cure rates after laser excision and laser ablation are similar. Topical agents are useful for persistent, multifocal lesions or for patients who cannot undergo surgical treatment. Imiquimod was associated with the lowest recurrence rate, highest human papillomavirus (HPV) clearance, and can be considered the best topical approach. Trichloroacetic acid and 5-fluorouracil are historical options and should be discouraged. For VaIN after hysterectomy for cervical intraepithelial neoplasia (CIN) 3, laser vaporization and topical agents are not the best options, since they cannot reach epithelium buried in the vaginal scar. In these cases surgical options are preferable. Brachytherapy has a high overall success rate but due to late side effects should be reserved for poor surgical candidates, having multifocal disease, and with failed prior treatments. VaIN tends to recur and ensuring patient adherence to close follow-up visits is of the utmost importance. The first evaluation should be performed at 6 months with cytology and an HPV test during 2 years and annually thereafter. The implementation of vaccination against HPV infection is expected to contribute to the prevention of VaIN and thus cancer of the vagina. The effects of treatment can have an impact on quality of life and result in psychological and psychosexual issues which should be addressed. Patients with VaIN need clear and up-to-date information on a range of treatment options including risks and benefits, as well as the need for follow-up and the risk of recurrence.

Disease severity scoring systems in mucosal lichen planus: A systematic review.

Several scoring systems have been developed to evaluate disease severity in mucosal lichen planus, but only a few have been validated to ensure reproducible and accurate assessment of disease severity. The current systematic review was undertaken to identify clinical severity scoring systems in mucosal lichen planus that have undergone validity or reliability testing and to describe their operating characteristics. We performed a bibliographic search in five databases from their inception to October 2022 for severity scoring systems in mucosal lichen planus that have undergone validity or reliability tests. Quality assessment was conducted using the Joanna Briggs Institute Critical Appraisal tools. We have included 118 studies and identified 11 clinical severity scoring systems for oral lichen planus that have undergone validity or reliability testing. Of these, the most reported were the Thongprasom score, the Oral Disease Severity Score (ODSS) and the REU (Reticular/hyperkeratotic, Erosive/erythematous, Ulcerative) scoring systems. We did not identify clinical scoring systems for extraoral mucosal lichen planus that have undergone validity or reliability testing. The ODSS and REU scoring systems have undergone the highest number of validation attempts and reliability assessments for oral lichen planus respectively. However, we have identified numerous factors that have hampered the universal adoption of a standardised scoring system. There is a need for the development and validation of scoring systems for extraoral mucosal lichen planus.

The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) Consensus Statement on the Management of Vaginal Intraepithelial Neoplasia.

ABSTRACT: The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vaginal intraepithelial neoplasia (VaIN). The management of VaIN varies according to the grade of the lesion: VaIN 1 (low grade vaginal squamous intraepithelial lesions (SIL)) can be subjected to follow-up, while VaIN 2-3 (high-grade vaginal SIL) should be treated. Treatment needs individualization according to the patient's characteristics, disease extension and previous therapeutic procedures. Surgical excision is the mainstay of treatment and should be performed if invasion cannot be excluded. Total vaginectomy is used only in highly selected cases of extensive and persistent disease. Carbon dioxide (CO2) laser may be used as both an ablation method and an excisional one. Reported cure rates after laser excision and laser ablation are similar. Topical agents are useful for persistent, multifocal lesions or for patients who cannot undergo surgical treatment. Imiquimod was associated with the lowest recurrence rate, highest human papillomavirus (HPV) clearance, and can be considered the best topical approach. Trichloroacetic acid and 5-fluorouracil are historical options and should be discouraged. For VaIN after hysterectomy for cervical intraepithelial neoplasia (CIN) 3, laser vaporization and topical agents are not the best options, since they cannot reach epithelium buried in the vaginal scar. In these cases surgical options are preferable. Brachytherapy has a high overall success rate but due to late side effects should be reserved for poor surgical candidates, having multifocal disease, and with failed prior treatments. VaIN tends to recur and ensuring patient adherence to close follow-up visits is of the utmost importance. The first evaluation should be performed at 6 months with cytology and an HPV test during 2 years and annually thereafter. The implementation of vaccination against HPV infection is expected to contribute to the prevention of VaIN and thus cancer of the vagina. The effects of treatment can have an impact on quality of life and result in psychological and psychosexual issues which should be addressed. Patients with VaIN need clear and up-to-date information on a range of treatment options including risks and benefits, as well as the need for follow-up and the risk of recurrence.

The Impact of COVID-19 Pandemic on Screening Programs for Cervical Cancer Prevention Across Europe.

OBJECTIVE: The aim of the study was to estimate the impact of COVID-19 pandemic on the practice of cervical cancer screening in European countries. MATERIALS AND METHODS: A 3 rounds e-survey was conducted among the 31 European Federation for Colposcopy member countries during 2020. Each representative was asked to answer to each questionnaire for their own country. Questionnaires were not anonymous. The first questionnaire was sent in April 2020 and second and third in June and December 2020, respectively. RESULTS: Twenty five of the 31 European countries solicited responded. A total of 19 countries (70.4%) reported that screening for cervical cancer was suspended at least once during the 3 rounds of questionnaires. In addition, 11 countries reported stopping colposcopy and treatments for cervical precancerous lesions at least once during the 3 rounds of questionnaires. These situations evolved with time, with the highest rate of countries recommending suspension of screening, colposcopy, and treatments during the second round of the survey. At round 3, no country recommended screening, colposcopy, and treatment, and 12 countries (57.5%) reported normal screening was fully implemented. CONCLUSIONS: Our results suggest massive disruption in cervical cancer screening programs across Europe resulting from COVID-19 pandemic. Increase in the incidence of cervical cancer is to be expected.

The European response to the WHO call to eliminate cervical cancer as a public health problem.

The age-standardised incidence of cervical cancer in Europe varies widely by country (between 3 and 25/100000 women-years) in 2018. Human papillomavirus (HPV) vaccine coverage is low in countries with the highest incidence and screening performance is heterogeneous among European countries. A broad group of delegates of scientific professional societies and cancer organisations endorse the principles of the WHO call to eliminate cervical cancer as a public health problem, also in Europe. All European nations should, by 2030, reach at least 90% HPV vaccine coverage among girls by the age of 15 years and also boys, if cost-effective; they should introduce organised population-based HPV-based screening and achieve 70% of screening coverage in the target age group, providing also HPV testing on self-samples for nonscreened or underscreened women; and to manage 90% of screen-positive women. To guide member states, a group of scientific professional societies and cancer organisations engage to assist in the rollout of a series of concerted evidence-based actions. European health authorities are requested to mandate a group of experts to develop the third edition of European Guidelines for Quality Assurance of Cervical Cancer prevention based on integrated HPV vaccination and screening and to monitor the progress towards the elimination goal. The occurrence of the COVID-19 pandemic, having interrupted prevention activities temporarily, should not deviate stakeholders from this ambition. In the immediate postepidemic phase, health professionals should focus on high-risk women and adhere to cost-effective policies including self-sampling.

Correction: Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.

[This corrects the article DOI: 10.1371/journal.pgen.1006866.].

Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.

A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4%) of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.

The use, quality and effectiveness of pelvic examination in primary care for the detection of gynaecological cancer: a systematic review.

BACKGROUND: Urgent suspected cancer referral guidelines recommend that women with gynaecological cancer symptoms should have a pelvic examination (PE) prior to referral. We do not know to what extent GPs comply, their competency at PE, or if PE shortens the diagnostic interval. OBJECTIVES: We conducted a systematic review of the use, quality and effectiveness of PE in primary care for women with suspected gynaecological cancer. METHOD: PRISMA guidelines were followed. Three databases were searched using four terms: PE, primary care, competency and gynaecological cancer. Citation lists of all identified papers were screened independently for eligibility by two reviewers. Data extraction was performed in duplicate and independently. Paper quality was assessed using the relevant Critical Appraisal Skills Programme checklist. Emergent themes and contrasting issues were explored in a narrative ecological synthesis. MAIN FINDINGS: Twenty papers met the inclusion criteria. 52% or less of women with suspicious symptoms had a PE. No papers directly explored GPs' competence at performing PE. Pre-referral PE was associated with reduced diagnostic delay and earlier stage diagnosis. Ecological synthesis demonstrated a complex interplay between patient and practitioner factors and the environment in which examination is performed. Presenting symptoms are commonly misattributed by patients and practitioners resulting in misdiagnosis and lack of PE. CONCLUSION: We do not know if pre-referral PE leads to better outcomes for patients. PE is often not performed for women with gynaecological cancer symptoms, and evidence that it may result in earlier stage of diagnosis is weak. More research is needed.

HLA and KIR Associations of Cervical Neoplasia.

Background: Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods: Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13858 healthy controls of European decent. Results: The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10-9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10-8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10-9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10-5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions: Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism.

What influences GPs' use of pelvic examination? A qualitative investigation in primary care.

BACKGROUND: Omission of pelvic examination (PE) has been associated with diagnostic delay in women diagnosed with gynaecological cancer. However, PEs are often not carried out by GPs. AIM: To determine the perceptions of GPs about the role of PEs, the barriers to and facilitators of PEs, and GPs' experience of PEs in practice. DESIGN AND SETTING: Qualitative semi-structured interview study conducted in one health board in Scotland (mixed urban and rural) with an approximate population of 500 000. METHOD: Interviews were conducted face-to-face or by telephone between March and June 2019. Framework analysis used the COM-B behaviour change model concepts of capability, opportunity, and motivation. RESULTS: Data was compatible with all three domains of the COM-B framework. Capability related to training in and maintenance of skills. These went beyond carrying out the examination to interpreting it reliably. Opportunity related to the clinical environment and the provision of chaperones for intimate examination. Interviewees described a range of motivations towards or against PEs that were unrelated to either capability or opportunity. These all related to providing high-quality care, but this was defined in different ways: 'doing what is best for the individual', 'doctors examine', and 'GPs as pragmatists'. CONCLUSION: GPs' reasons for carrying out, or not carrying out, PEs in women with symptoms potentially indicating cancer are complex. The COM-B framework provides a way of understanding this complexity. Interventions to increase the use of PEs, and critics of its non-use, need to consider these multiple factors.

National guidelines for management of cervical squamous intraepithelial lesion: A survey of European Federation for colposcopy members.

OBJECTIVES: The management of women with cervical squamous intraepithelial lesions (SIL) is fundamental to prevention of cervical cancer in an organized cervical screening programme. Clinical guidance should improve quality of care and clinical effectiveness if developed and implemented appropriately. This survey provides an update on the current situation of national guidelines for management of cervical SIL amongst member countries of European Federation for Colposcopy (EFC). STUDY DESIGN: A questionnaire was sent to representatives of each member country of EFC. The questionnaire contained questions on: guidelines for management of cervical SIL of the National Societies/Associations of Colposcopy or others national societies/associations including the development and the consultation processes, guidelines for management of lower genital tract diseases and the regulations in each country for colposcopy practice. RESULTS: We received responses from all 34 member countries. Thirty countries reported a national guideline for management of cervical SIL that were developed by, or in conjunction with, their national societies or associations of colposcopy. In most cases there was adherence to the recommended steps for guideline development: they were developed by a multi-disciplinary group of specialists (29 countries) and society members were consulted before publication (21 countries). A small number of countries (8) reported to have guidelines for the management of lower genital tract dysplasia (e.g. vulval disease) developed by other national societies. In most countries (26) the colposcopists are obliged to follow the guidelines but this is regulated in only 6 and in 12 countries the colposcopists need to be certified by the national society of colposcopy in order to practice. CONCLUSION: There are advances in the development and provision of country specific guidance on the management of cervical SIL. Most EFC member countries have appropriate national guidelines that were developed using a clear methodology, are updated according to progresses in the field and are accessible online to current practitioners. These guidelines support colposcopists to follow evidence-based practice and provides understanding of best practice in guideline development and access.

After-effects reported by women following colposcopy, cervical biopsies and LLETZ: results from the TOMBOLA trial.

OBJECTIVE: Few studies have investigated physical after-effects of colposcopy. We compared post-colposcopy self-reported pain, bleeding, discharge and menstrual changes in women who underwent: colposcopic examination only; cervical punch biopsies; and large loop excision of the transformation zone (LLETZ). DESIGN: Observational study nested within a randomised controlled trial. SETTING: Grampian, Tayside and Nottingham. POPULATION: Nine hundred-and-twenty-nine women, aged 20-59, with low-grade cytology, who had completed their initial colposcopic management. METHODS: Women completed questionnaires on after-effects at approximately 6-weeks, and on menstruation at 4-months, post-colposcopy. MAIN OUTCOME MEASURES: Frequency of pain, bleeding, discharge; changes to first menstrual period post-colposcopy. RESULTS: Seven hundred-and-fifty-one women (80%) completed the 6-week questionnaire. Of women who had only a colposcopic examination, 14-18% reported pain, bleeding or discharge. Around half of women who had biopsies only and two-thirds treated by LLETZ reported pain or discharge (biopsies: 53% pain, 46% discharge; LLETZ: 67% pain, 63% discharge). The frequency of bleeding was similar in the biopsy (79%) and LLETZ groups (87%). Women treated by LLETZ reported bleeding and discharge of significantly longer duration than other women. The duration of pain was similar across management groups. Forty-three percent of women managed by biopsies and 71% managed by LLETZ reported some change to their first period post-colposcopy, as did 29% who only had a colposcopic examination. CONCLUSIONS: Cervical punch biopsies and, especially, LLETZ carry a substantial risk of after-effects. After-effects are also reported by women managed solely by colposcopic examination. Ensuring that women are fully informed about after-effects may help to alleviate anxiety and provide reassurance, thereby minimising the harms of screening.

After-effects reported by women having follow-up cervical cytology tests in primary care: a cohort study within the TOMBOLA trial.

BACKGROUND: Although it is recognised that some women experience pain or bleeding during a cervical cytology test, few studies have quantified physical after-effects of these tests. AIM: To investigate the frequency, severity, and duration of after-effects in women undergoing follow-up cervical cytology tests, and to identify subgroups with higher frequencies in Grampian, Tayside, and Nottingham. DESIGN: Cohort study nested with a multi-centre individually randomised controlled trial. METHOD: The cohort included 1120 women, aged 20-59 years, with low-grade abnormal cervical cytology who completed a baseline sociodemographic questionnaire and had a follow-up cervical cytology test in primary care 6 months later. Six weeks after this test, women completed a postal questionnaire on pain, bleeding, and discharge experienced after the test, including duration and severity. The adjusted prevalence of each after-effect was computed using logistic regression. RESULTS: A total of 884 women (79%) completed the after-effects questionnaire; 30% of women experienced one or more after-effect: 15% reported pain, 16% bleeding, and 7% discharge. The duration of discharge was ≤2 days for 66%, 3-6 days for 22%, and ≥7 days for 11% of women. Pain or bleeding lasted ≤2 days in more than 80% of women. Severe after-effects were reported by <1% of women. The prevalence of pain decreased with increasing age. Bleeding was more frequent among nulliparous women. Discharge was more common among oral contraceptive users. CONCLUSION: Pain, bleeding, and discharge are not uncommon in women having follow-up cervical cytology tests. Informing women about possible after-effects could better prepare them and provide reassurance, thereby minimising potential non-adherence with follow-up or non-participation with screening in the future.

Cervical screening in women over the age of 50: results of a population-based multicentre study.

OBJECTIVE: It has been suggested that women over 50 with a satisfactory negative smear history are at low risk for dyskaryosis and might be suitable for withdrawal from the cervical screening programme. The objectives of this study are to document the pattern of dyskaryosis in the cervical smears of women over 50 and to relate the risk of dyskaryosis in these women to the prior smear history. DESIGN: Available computerised smear data were analysed. SETTING: Five regions in England and Scotland; Aberdeen, Dundee, Birmingham, Gateshead and Nottingham. POPULATION: All women aged 50 or over who had a satisfactory smear between 1988 and 1996. METHODS: Smear results were sorted into individual smear records. The first smear after the age of 50 was identified as well as all smears before and after the age of 50. MAIN OUTCOME MEASUREMENTS: The smear history before and after the age of 50 was determined for all women. The relative risk of dyskaryosis as well as the time to dyskaryosis was calculated for women whose raw data were available. RESULTS: The study included 170,436 women with at least one satisfactory smear after 50. No results of previous smears were available in 90,546 (54%) of women but 36,512 (21%) of women had a satisfactory negative smear history. Women with prior dyskaryosis or borderline nuclear abnormalities (BNA) had an increased risk of dyskaryosis after the age of 50 compared with women with a negative history (RR 4.39 and 3.08 respectively). It was notable that 1.8% of women with a negative history still demonstrated subsequent dyskaryosis. CONCLUSIONS: Women with either dyskaryosis or BNA before 50 are not suitable for withdrawal from cervical screening. Well-screened women with a negative smear history at the age 50 still have a residual risk of subsequently developing a new abnormality.