Metaproteomic analysis from cervical biopsies and cytologies identifies proteinaceous biomarkers representing both human and microbial species.

The detection of HPV infection and microbial colonization in cervical lesions is currently done through PCR-based viral or bacterial DNA amplification. Our objective was to develop a methodology to expand the metaproteomic landscape of cervical disease and determine if protein biomarkers from both human and microbes could be detected in distinct cervical samples. This would lead to the development of multi-species proteomics, which includes protein-based lateral flow diagnostics that can define patterns of microbes and/or human proteins relevant to disease status. In this study, we collected both non-frozen tissue biopsy and exfoliative non-fixed cytology samples to assess the consistency of detecting human proteomic signatures between the cytology and biopsy samples. Our results show that proteomics using biopsies or cytologies can detect both human and microbial organisms. Across patients, Lumican and Galectin-1 were most highly expressed human proteins in the tissue biopsy, whilst IL-36 and IL-1RA were most highly expressed human proteins in the cytology. We also used mass spectrometry to assess microbial proteomes known to reside based on prior 16S rRNA gene signatures. Lactobacillus spp. was the most highly expressed proteome in patient samples and specific abundant Lactobacillus proteins were identified. These methodological approaches can be used in future metaproteomic clinical studies to interrogate the vaginal human and microbiome structure and metabolic diversity in cytologies or biopsies from the same patients who have pre-invasive cervical intraepithelial neoplasia, invasive cervical cancer, as well as in healthy controls to assess how human and pathogenic proteins may correlate with disease presence and severity.

Clinical performance of primary HPV screening cut-off for colposcopy referrals in HPV-vaccinated cohort: Observational study.

OBJECTIVE: To understand the effect of changing from cytology-based to primary HPV screening on the positive predictive value (PPV) of colposcopy referrals for cervical intraepithelial neoplasia (CIN) in a cohort offered HPV vaccination. DESIGN: Retrospective pre/post observational cohort study. SETTING: Scotland. POPULATION OR SAMPLE: 2193 women referred to colposcopy between September 2019 and February 2020 from cytology-based screening and between September 2020 and February 2021 from primary high-risk HPV (hrHPV) screening. METHODS: Calculating positive predictive values (PPVs) for two cohorts of women; one having liquid-based cytology screening and the other, the subsequent hrHPV cervical screening as a pre/post observational study. MAIN OUTCOME MEASURES: Positive predictive values of LBC and hrHPV cut-offs for colposcopy referral for CIN at colposcopy. RESULTS: Three papers fitted our criteria; these reported results only for cytology-based screening. The PPV was lower for women in HPV-vaccinated cohorts indicating a lower prevalence of disease. Vaccination under the age of 17 had the lowest PPV reported. Scottish colposcopy data concerning hrHPV and cytology showed a non-significant difference between PPV (17.5%, 95% CI 14.3-20.7, and 20.6, 95% CI 16.7-24.5, respectively) for referrals with a cut-off of low grade dyskaryosis (LGD); both met the standard set of 8-25%. The hrHPV PPV (66.7, 95% CI 56.8-76.6) was comparable to cytology (64.1, 95% CI 55.8-72.4) for referrals with a cut-off of high grade dyskaryosis (HGD) but neither met the standard set of 77-92%. CONCLUSIONS: Current literature only provides PPVs for LBC and, overall, the vaccinated cohort had lower PPVs. Only LG dyskaryosis met PHE criteria. The PPV for HPV-vaccinated women undergoing either LBC or HR-HPV screening were not statistically different. However, similar to papers in the current literature, HG dyskaryosis (HGD) PPVs of both techniques did not meet the PHE threshold of 76.6-91.6% outlined in the cervical standards data report.

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 statements on pre-invasive vulvar lesions.

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 vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).

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 Statements on Pre-invasive Vulvar Lesions.

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 vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).

Invasive cervical cancer following treatment of pre-invasive lesions: A potential theory based on a small case series.

PURPOSE: The aim of this study is to present a single department's experience on cervical cancer cases following previous excision of cervical intraepithelial neoplasia (CIN) and to discuss potential pathogenesis. METHODS: Nine cervical cancer cases meeting the inclusion criteria, with available pathological and follow-up data, were considered eligible for this study. RESULTS: The majority (7/9) have had clear excisional margins. The interval between initial treatment and cancer diagnosis ranged from 7 to 17 years. In all cases cancer diagnosis was "unexpected", as the prior cytological and/or colposcopic evaluation was not suggestive of significant cervical pathology. All cancers were squamous, and 5/9 at stage I. CONCLUSION: The long interval between initial CIN treatment and final diagnosis as well as the normal post-treatment follow-up may suggest a 'de novo' underlying but 'hidden' carcinogenesis process. It might be that dysplastic cells entrapped within crypts (or normal metaplastic affected by the same predisposing factors) continue undergoing their evolution, undetectable by cytology and colposcopy until they invade stroma and surfaces (endo- and/or ectocervical) approximately a decade later. Heavy cauterisation of cervical crater produced post excision might be a potential culprit of this entrapment.

Has the human papillomavirus (HPV) immunization programme improved obstetric outcomes in spontaneous delivery? An ecological study.

OBJECTIVE: To measure the rates of adverse obstetric outcomes in spontaneous delivery in a population of young women with high uptake of the bivalent human papillomavirus (HPV) vaccine. STUDY DESIGN: This was a population-based ecological study with data from the Aberdeen Maternity and Neonatal Databank, UK. All women born between 1986-1996 with spontaneous singleton live birth at age 20-30 years were included for analysis. Exposure was defined according to maternal year of birth and HPV immunisation eligibility: pre-immunisation cohort (1986-1990), catch-up immunisation cohort (1991-1994) and routine immunisation cohort (1995-1996). Outcomes were defined as spontaneous preterm birth (PTB), low birth weight (LBW) and pre-labour preterm rupture of membranes (pPROM). Generalized estimating equation models were applied, adjusted for deprivation, smoking status, marital status, body mass index, parity, maternal age and year of infant delivery. RESULTS: A total of 6515 spontaneous singleton live births were included in final analysis, with 5134 births included in the pre-immunisation cohort, 1250 in the catch-up immunisation cohort and 131 in the routine immunisation cohort. Compared with the pre-immunisation cohort, no statistically significant reduction on PTB, LBW or pPROM were observed in either immunised cohorts. The adjusted odds ratio (aOR) on PTB was 0.64 (95 % confidence interval, 0.40-1.03) in the catch-up cohort and 0.71 (0.28-1.77) in the routine cohort. The corresponding aOR were 0.88 (0.54-1.45) and 0.51 (0.16-1.62) for LBW and 1.62 (0.58-4.54) and 1.51 (0.21-11.01) for pPROM. CONCLUSIONS: We did not observe a significant reduction on PTB, LBW or pPROM among spontaneous singleton live birth in either HPV immunised cohorts, although the additional benefit in improving obstetric outcomes cannot be excluded because of the limits of the sample size and the study design. Further demonstration is warranted when more women in the fully HPV immunised cohorts embark on pregnancy.

Options for triage and implications for colposcopists within European HPV-based cervical screening programmes.

The development of human papillomavirus (HPV)-based screening should detect more pre-cancerous changes and so reduce the incidence and mortality from cervical squamous carcinoma and cervical adenocarcinoma. However, many more women are high risk HPV (hrHPV) screen positive compared to cytology-based screening, especially in younger age-women. A variety of tests have become available which may triage into those hrHPV test-positive women who need immediate referral to colposcopy from those who need early repeat HPV tests or recall on the basis of their disease status. We performed a literature review of publications and a manual search from 2010, reporting cytology, HPV partial genotyping, dual-staining and DNA methylation for triage of hrHPV positive tests, including their comparative performance between these methods as well as the effectiveness of some triage combinations with reference to HPV-based screening services in Europe. Cost effectiveness and the structure of triage algorithms for colposcopists also have been considered. From one report evaluating four options for triage as single options or as combined algorithms, partial genotyping for HPV 16 and 18 with dual-staining yielded the highest risk of cervical intraepithelial neoplasia grade three or worse within an HPV positive population and with an acceptable colposcopy rate. From a separate paper, this option appeared cost effective. However, publications were difficult to compare objectively. All options have their merits but a combination triage involving any two of cytology, HPV partial genotyping or dual-staining seems most efficient at present. HPV vaccination may impact upon the performance of future partial genotyping. DNA Methylation may become an acceptable future option.

Effect of Sequential Rounds of Cervical Cancer Screening on Management of HPV-positive Women: A 15-year Population-based Cohort Study from China.

Women are anticipated to go through more than two rounds of cervical screening in their lifetime. Human papillomavirus (HPV) testing is increasingly used as the primary cervical cancer screening test. However, triage strategies for HPV-positive women were usually evaluated at baseline screening. We assessed the effect of sequential rounds of cervical screening on several algorithms for HPV triage. A total of 1,997 women ages 35-45 years were enrolled in 1999 in Shanxi, P.R. China and followed up three times at approximately 5-year intervals. Cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+) prevalence by prior HPV results and performance of 12 triage algorithms with cytology, genotyping, and prior HPV were examined among 229 HPV-positive women at the fourth round. CIN2+ prevalence varied from 56.5% (95% confidence interval, 36.8%-74.4%) following 15 years HPV persistence to 3.5% (1.2%-9.9%) with an incident HPV within 15 years. Triage with cytology (with threshold of atypical squamous cells of undetermined significance) yielded positive predictive value (PPV) of 21.4% (13.8%-29.0%), entailing immediate colposcopic referral, and negative predictive value (NPV) of 97.4% (94.6%-100%), permitting retesting at short intervals. Triage with genotyping (16/18/31/33/45/52/58) or prior HPV results showed comparable performance with cytology. Among 11 triage algorithms with similar NPV to cytology, triage with prior HPV results and reflex genotyping (16/18) achieved highest PPV of 28.9% (18.8%-39.1%) and lowest colposcopy referral of 33.2% (27.4%-39.5%). HPV persistence across rounds is an effective risk stratifier in HPV-positive women. Mainstream cytology and genotyping, with or without consideration of prior HPV results, remain effective for HPV triage at fourth round. PREVENTION RELEVANCE: The study highlights the sustained effectiveness of mainstream HPV triage methods, such as cytology and genotyping, after sequential rounds of cervical screening. It also suggests that use of HPV persistence across rounds can improve management of HPV-positive women in cervical cancer screening.

UK national survey of the management of vaginal intraepithelial neoplasia.

Vaginal intraepithelial neoplasia (VaIN) is less common than intraepithelial neoplasia at other non-cervical sites and can be challenging to manage. This survey describes current clinical practice by colposcopists in the UK. An online questionnaire was emailed to all the lead colposcopists in U.K. A total of 86 (43%) responses were obtained. The median number of cases of VaIN seen in a year was five (range 0-100. Most clinics (95%) managed low grade VaIN conservatively. Local vaginal mucosal excision was the most common surgical procedure. Half of respondents adopted observation, although 64% of the units referred cases to a cancer centre. More than half used a combination of cytology and colposcopy for follow-up; only two reported using Human papilloma virus testing. Seventy-seven of eighty-six lead colposcopists did not have a local guideline and would support national guidance. Treatment differed across the UK with no agreed management guidelines.Impact statementWhat is already known on the subject? Vaginal intraepithelial neoplasia (VaIN) is a pre-cancerous condition of lower genital tract and usually co-exists with cervical intraepithelial neoplasia (CIN) rather than in isolation. Unlike CIN, VaIN can be extremely challenging to manage in view of its anatomical proximity to bladder and bowel and also difficulty in accessing fornices. If diagnosed during the definitive management of CIN at the time of hysterectomy and confined to the upper vagina, it could be surgically treated at the same time. VaIN can be more challenging post-hysterectomy, especially following a failed medical and conservation option. Various treatment options are adopted for management of VaIN with no standardisation of care.What do the results of this study add? A national survey was conducted to assess the management of VaIN amongst lead colposcopists. The national survey has added valuable results, despite a response rate of only 43%. The survey confirmed conservative approach to low grade VaIN but differing treatment for high grade VaIN.What are the implications of these findings for clinical practice and/or further research? This clearly calls for the implementation of a national guideline in the UK to standardise management of VaIN, though it may be quite challenging. The survey could help inform implementation of HrHPV testing in recurrent or persistent VaIN.

Women's preferences for communication with the cervical screening programme: A qualitative study.

BACKGROUND: In Scotland, invitations and results for cervical screening are sent by post. We ask the question: is this an effective means of communication in the 21st century? Consideration of other ways of communicating with women may help to increase acceptability of the cervical screening programme. OBJECTIVE: To explore perspectives of screening-eligible women, regarding methods for communication of invitations and results from the cervical screening programme to improve acceptability. METHODS: A qualitative study design using semi-structured face-to-face or telephone interviews with women aged 25-65 years. Thirty interviews were directed using visual cues to generate discussion. Interviews were audio-recorded and transcribed verbatim. Thematic analysis of the data was conducted using a Framework approach. RESULTS: The main advantage of the postal system is its perceived formality; however, its lack of speed was a concern. Advantages of e-communication included speed and convenience; however, concerns such as lack of confidentiality and access were mentioned. Telephone communication was deemed impractical, while face-to-face communication was highly regarded. Furthermore, the majority of participants felt screening appointments set at a specific date and time may improve uptake. Overall, participants believed there is no universal solution regarding the issue of communication. CONCLUSION: At present, the postal system may be an appropriate method for invitation and results for cervical screening; however, there may be greater scope for preference of communication to improve the acceptability of the screening programme to women.

Preferences for interventions designed to increase cervical screening uptake in non-attending young women: How findings from a discrete choice experiment compare with observed behaviours in a trial.

BACKGROUND: Young women's attendance at cervical screening in the UK is continuing to fall, and the incidence of invasive cervical cancer is rising. OBJECTIVES: We assessed the preferences of non-attending young women for alternative ways of delivering cervical screening. DESIGN: Postal discrete choice experiment (DCE) conducted during the STRATEGIC study of interventions for increasing cervical screening uptake. Attributes included action required to arrange a test, location of the test, availability of a nurse navigator and cost to the National Health Service. SETTING AND PARTICIPANTS: Non-attending young women in two UK regions. MAIN OUTCOME MEASURES: Responses were analysed using a mixed multinomial logit model. A predictive analysis identified the most preferable strategy compared to current screening. Preferences from the DCE were compared with observed behaviours during the STRATEGIC trial. RESULTS: The DCE response rate was 5.5% (222/4000), and 94% of respondents agreed screening is important. Preference heterogeneity existed around attributes with strong evidence for test location. Relative to current screening, unsolicited self-sampling kits for home use appeared most preferable. The STRATEGIC trial showed this same intervention to be most effective although many women who received it and were screened, attended for conventional cytology instead. CONCLUSIONS: The DCE and trial identified the unsolicited self-sampling kit as the most preferred/effective intervention. The DCE suggested that the decision of some women receiving the kit in the trial to attend for conventional cytology may be due to anxieties around home testing coupled with a knowledge that ignoring the kit could potentially have life-changing consequences.

Risk of newly detected infections and cervical abnormalities in adult women seropositive or seronegative for naturally acquired HPV-16/18 antibodies.

BACKGROUND: Infections with human papillomavirus (HPV) types 16 and 18 account for ~70% of invasive cervical cancers but the degree of protection from naturally acquired anti-HPV antibodies is uncertain. We examined the risk of HPV infections as defined by HPV DNA detection and cervical abnormalities among women >25 years in the Human Papilloma VIrus Vaccine Immunogenicity ANd Efficacy trial's (VIVIANE, NCT00294047) control arm. METHODS: Serum anti-HPV-16/18 antibodies were determined at baseline and every 12 months in baseline DNA-negative women (N = 2687 for HPV-16 and 2705 for HPV-18) by enzyme-linked immunosorbent assay (ELISA) from blood samples. HPV infections were identified by polymerase chain reaction (PCR) every 6-months, and cervical abnormalities were confirmed by cytology every 12 months. Data were collected over a 7-year period. The association between the risk of type-specific infection and cervical abnormalities and serostatus was assessed using Cox proportional hazard models. RESULTS: Risk of newly detected HPV-16-associated 6-month persistent infections (PI) (hazard ratio [HR] = 0.56 [95%CI:0.32; 0.99]) and atypical squamous cells of undetermined significance (ASC-US+) (HR = 0.28 [0.12; 0.67]) were significantly lower in baseline seropositive vs baseline seronegative women. HPV-16-associated incident infections (HR = 0.81 [0.56; 1.16]) and 12-month PI (HR = 0.53 [0.24; 1.16]) showed the same trend. A similar trend of lower risk was observed in HPV-18-seropositive vs -seronegative women (HR = 0.95 [0.59; 1.51] for IIs, HR = 0.43 [0.16; 1.13] for 6-month PIs, HR = 0.31 [0.07; 1.36] for 12-month PIs, and HR = 0.61 [0.23; 1.61] for ASC-US+). CONCLUSIONS: Naturally acquired anti-HPV-16 antibodies were associated with a decreased risk of subsequent infection and cervical abnormalities in women >25 years. This possible protection was lower than that previously reported in 15- to 25-year-old women.

Prevalence of cervical disease at age 20 after immunisation with bivalent HPV vaccine at age 12-13 in Scotland: retrospective population study.

OBJECTIVE: To quantify the effect on cervical disease at age 20 years of immunisation with bivalent human papillomavirus (HPV) vaccine at age 12-13 years. DESIGN: Retrospective population study, 1988-96. SETTING: National vaccination and cervical screening programmes in Scotland. PARTICIPANTS: 138 692 women born between 1 January 1988 and 5 June 1996 and who had a smear test result recorded at age 20. MAIN OUTCOME MEASURES: Effect of vaccination on cytology results and associated histological diagnoses from first year of screening (while aged 20), calculated using logistic regression. RESULTS: 138 692 records were retrieved. Compared with unvaccinated women born in 1988, vaccinated women born in 1995 and 1996 showed an 89% reduction (95% confidence interval 81% to 94%) in prevalent cervical intraepithelial neoplasia (CIN) grade 3 or worse (from 0.59% (0.48% to 0.71%) to 0.06% (0.04% to 0.11%)), an 88% reduction (83% to 92%) in CIN grade 2 or worse (from 1.44% (1.28% to 1.63%) to 0.17% (0.12% to 0.24%)), and a 79% reduction (69% to 86%) in CIN grade 1 (from 0.69% (0.58% to 0.63%) to 0.15% (0.10% to 0.21%)). Younger age at immunisation was associated with increasing vaccine effectiveness: 86% (75% to 92%) for CIN grade 3 or worse for women vaccinated at age 12-13 compared with 51% (28% to 66%) for women vaccinated at age 17. Evidence of herd protection against high grade cervical disease was found in unvaccinated girls in the 1995 and 1996 cohorts. CONCLUSIONS: Routine vaccination of girls aged 12-13 years with the bivalent HPV vaccine in Scotland has led to a dramatic reduction in preinvasive cervical disease. Evidence of clinically relevant herd protection is apparent in unvaccinated women. These data are consistent with the reduced prevalence of high risk HPV in Scotland. The bivalent vaccine is confirmed as being highly effective vaccine and should greatly reduce the incidence of cervical cancer. The findings will need to be considered by cervical cancer prevention programmes worldwide.

Increased risk of HPV-associated genital cancers in men and women as a consequence of pre-invasive disease.

To assess the excess risk of HPV-associated cancer (HPVaC) in two at-risk groups-women with a previous diagnosis of high grade cervical intraepithelial neoplasia (CIN3) and both men and women treated for non-cervical pre-invasive anogenital disease. All CIN3 cases diagnosed in 1989-2015 in Scotland were extracted from the Scottish cancer registry (SMR06). All cases of pre-invasive penile, anal, vulval, and vaginal disease diagnosed in 1990-2015 were identified within the NHS pathology databases in the two largest NHS health boards in Scotland. Both were linked to SMR06 to extract subsequent incidence of HPVaC following the diagnosis of CIN3 or pre-invasive disease. Standardised incidence ratios were calculated for the risk of acquiring HPVaC for the two at-risk groups compared to the general Scottish population. Among 69,714 females in Scotland diagnosed with CIN3 (890,360.9 person-years), 179 developed non-cervical HPVaC. CIN3 cases were at 3.2-fold (95% CI: 2.7 to 3.7) increased risk of developing non-cervical HPVaC, compared to the general female population. Among 1,235 patients diagnosed with non-cervical pre-invasive disease (9,667.4 person-years), 47 developed HPVaC. Individuals with non-cervical pre-invasive disease had a substantially increased risk of developing HPVaC - 15.5-fold (95% CI: 11.1 to 21.1) increased risk for females and 28-fold (11.3 to 57.7) increased risk for males. We report a significant additional risk of HPV-associated cancer in those have been diagnosed with pre-invasive HPV-associated lesions including but not confined to the cervix. Uncovering the natural history of pre-invasive disease has potential for determining screening, prevention and treatment.

Information needs of young women vaccinated against HPV attending colposcopy: a qualitative study.

BACKGROUND: Previous studies have shown that woman attending their first cervical screening or colposcopy appointment experience negative emotions, primarily anxiety and fear. With the introduction of the Human Papillomavirus (HPV) vaccine, it is unknown whether these emotions will have altered or whether the information needs of vaccinated women will have changed. The objective of this study is to determine the knowledge, understanding and concerns that young women have about HPV when attending colposcopy and whether their information needs are met. METHODS: This is a qualitative study using semi-structured interviews which were audiotaped and transcribed. Data was analysed thematically, with recruitment until data saturation was reached. Women born after 01/09/1990 and attending colposcopy as a result of abnormal cytology were eligible to join the study. Recruitment took place in an out-patient regional colposcopy clinic, Aberdeen, Scotland. RESULTS: Fifteen women were interviewed. The majority of participants had some knowledge and understanding of HPV, cervical screening and colposcopy. Knowledge about the HPV vaccine was more limited; a third of participants misunderstood the effectiveness of the vaccine believing that is provided complete protection, and were left feeling that it had failed them. Some also felt that they were "test cases" for the vaccine. CONCLUSION: With the introduction of the HPV vaccine, the information and support needs of young women attending colposcopy are not fully met, leaving women with unanswered questions. With increasing numbers of vaccinated women entering the screening programme, it is timely to review the information available to these women.

Effect of High-Risk Human Papillomavirus but Normal Cytology at Test of Cure on Achieving Colposcopy Standards.

OBJECTIVE: In United Kingdom., test of cure after treatment of any grade of cervical intraepithelial neoplasia (CIN) incorporates high-risk human papillomavirus (Hr-HPV) test and cytology at 6-month follow-up. The aims of the study were to determine the rate of recurrent CIN in women who are Hr-HPV positive and cytology negative and to explore possible associated risk factors. METHODS: A retrospective observational cohort study was performed in women treated for any grade CIN between 2010 and 2015 from a regional population, who were Hr-HPV positive and cytology negative at first follow-up. RESULTS: A total of 2729 women were identified as treated for any grade CIN, and 213 (7.8%) were re-referred to colposcopy having Hr-HPV-positive test and negative cytology at test of cure. Their mean age was 31.56 years (range = 19-62 years). The mean time of follow-up per woman was 30.50 months (range = 2-63 months). At colposcopy, 171 (80.3%) had colposcopy examination only and 42 women (19.7%) had a biopsy. Twenty-four cases (11.3%) of CIN were identified of which 4 (1.9%) were CIN 2/3. Eleven women (5.2%) in total had a repeat treatment. Five women (2.3%) had biopsy-proven CIN 2/3 within 12-months after treatment. No cases of CIN 3+ after negative colposcopy were identified during the follow-up period. CONCLUSIONS: The incorporation of Hr-HPV testing yielded a very small number of women with residual CIN within 12 months of treatment. Our results suggest that women who are Hr-HPV positive and cytology negative after treatment of CIN with normal and adequate colposcopy could be discharged to routine recall if confirmed by larger national data.