Low-grade Smears Research Articles

Prevalence and Description of High-Grade Intraepithelial Lesions of Cervical Mucosa Cells in a Screening Programme for Cervical Cancer in Isère, France.

This study aims to analyse high-grade intraepithelial lesions (LIEHG) observed in a screening programme from 2010 to 2018 to more accurately describe them and formulate recommendations for best practices in the context of screening evolution following the introduction of an HPV test in primary cervical cancer screening in 2020. This study included 305,940 asymptomatic women aged 25-65 years. The eligible population was invited to undergo a screening cervico-uterine-smear every 3 years. If this smear was normal, the woman received a new invitation. In the case of a positive screen, the patient underwent further diagnostic procedures, such as colposcopy and biopsy to confirm the diagnosis. Only those diagnosed with LIEHG and above proceeded to treatment. The diagnoses associated with LIEHG were those related to the WHO Classification of tumours of the uterine cervix. Positive smears led to the diagnosis of 3230 LIEHG. The prevalence of LIEHG in the screened population was 0.4%. The LIEHG distribution varied significantly according to the age of the women. The probability of diagnosing LIEHG in young women was 12.2% at 25-29 years. This probability decreased by half after 50 years. We observed that the type of smear was significantly associated with LIEHG detection. The positive predictive value for diagnosing LIEHG was 70.3% for high-grade squamous intraepithelial lesion (HSIL) smears and 35.1% for atypical squamous cells cannot exclude HSIL (ASC-H) smears. In the study population, the prevalence of LIEHG was high in women under 35 years. Low-grade smears were correlated with the risk of LIEHG and should prompt screening facilities to allocate resources to ensure active follow-up of LSIL and ASC-US smears. Adherence to cytological screening recommendations was associated with a reduced risk of LIEHG in multivariate analysis.

Comparison of HPV 16/18 Genotyping and p16/Ki67 Dual Staining for Detection of High-Grade Cervical Lesion in Patients with Low-Grade Cervical Smears.

To triage low-grade cervical smears (ASCUS/LSIL) by HPV 16/18 genotyping and dual staining with p16/Ki67 and to compare the sensitivity and specificity of these two triage methods for detection of high-grade cervical intraepithelial neoplasia (HGCIN). In this prospective cross-sectional study, we evaluated a total of 89 women with low-grade smears (54 ASCUS, 35 LSIL) recruited from a tertiary care hospital. All patients underwent colposcopy guided cervical biopsy. Histopathology was used as gold standard. All samples were subjected to HPV 16/18 genotyping (excluding 9) using DNA PCR and p16/Ki67 dual staining (excluding 4) using Roche® kit. We then compared the two triage methods to detect high-grade cervical lesions. Overall, in all low-grade smears sensitivity, specificity and accuracy of HPV 16/18 genotyping, was found to be 66.7%, 77.1% and 76.2% respectively (p = 0.03). In low-grade smears sensitivity, specificity and accuracy of dual staining, was found to be 66.7%, 84.8% and 83.5% respectively (p = 0.01). Overall, in all low-grade smears the sensitivity of the two tests was comparable. However, dual staining had a higher specificity and accuracy than HPV 16/18 genotyping. It was concluded that both are effective triage methods but dual staining had a better performance than HPV 16/18 genotyping.

Protocol for Compass: a randomised controlled trial of primary HPV testing versus cytology screening for cervical cancer in HPV-unvaccinated and vaccinated women aged 25–69 years living in Australia

IntroductionAustralia’s National Cervical Screening Program (NCSP) currently recommends 2-year cytology in women aged 18–69 years. Following a review of the NCSP prompted by the implementation of human papillomavirus (HPV) vaccination,...

Association between grade of referral smear and high-grade disease among women with biopsy samples showing cervical intraepithelial neoplasia grade 2.

To determine whether the grade of referral smear reflects the frequency of cervical intraepithelial neoplasia (CIN) grade 3 (CIN3) or worse lesions among patients with CIN2 on punch biopsy. In a retrospective study, data were reviewed from women with a punch biopsy sample showing CIN2 and a known referral smear who underwent large loop excision of the transformation zone (LLETZ) between January 1, 2013, and January 1, 2016, at Galway University Hospital, Ireland. Data were analyzed by patient age (≤30 and >30years), referral smear (low and high grade), and LLETZ histology (≤CIN2 and ≥CIN3). Overall, 264 women were included. LLETZ histology of CIN3 or worse was more common among women with high-grade referral smears (63/144 [43.8%]) than among those with low-grade smears (26/120 [21.7%]; relative risk 2.02, 95% confidence interval 1.37-2.96; P<0.001). Among patients younger than 30years, underlying CIN3 and above was again more frequent among women with high-grade (44/95 [46.3%]) versus low-grade smears (12/56 [21.4%]; relative risk 2.16, 95% confidence interval 1.25-3.73; P=0.004). No difference was recorded in the older age group. Although LLETZ can be performed for a CIN2 biopsy and high-grade smear, consideration should be given among young women (<30years) with low-grade smears whose biopsy histology is incidentally CIN2.

The role of human papillomavirus test after conization for CIN3 in predicting residual disease

Screening for cervical cancer precursors by cytology has been very successful in countries where adequate resources exist to ensure high quality and good coverage of the population at risk. Mortality reductions in excess of 50% have been achieved in many developed countries; however the procedure is generally inefficient and unworkable in many parts of the world where the appropriate infrastructure is not achievable.A summary and update of recently published meta-analyses and systematic reviews on four possible clinical applications of human papillomavirus (HPV) DNA testing is provided in this article: (1) triage of women with equivocal or low-grade cytological abnormalities; (2) follow-up of women with abnormal screening results who are negative at colposcopy/biopsy; (3) prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN), and most importantly (4) primary screening HPV DNA test, solely or in combination with Pap smear to detect cervical cancer precursors. There are clear benefits for the use of HPV DNA testing in the triage of equivocal smears, low-grade smears in older women and in the post-treatment surveillance of women after treatment for CIN. However, there are still issues regarding how best to use HPV DNA testing in primary screening. Primary screening with Hybrid Capture® 2 (HC2) generally detects more than 90% of all CIN2, CIN3 or cancer cases, and is 25% (95% CI): 15–36%) relatively more sensitive than cytology at a cut-off of abnormal squamous cells of undetermined significance (ASC-US) (or low-grade squamous intraepithelial lesions (LSIL) if ASC-US unavailable), but is 6% (95% CI: 4–7%) relatively less specific. Several approaches are currently under evaluation to deal with the lower specificity of HPV DNA testing as associated with transient infection. These include HPV typing for HPV-16 and -18/45, markers of proliferative lesions such as p16 and mRNA coding for the viral E6 and/or E7 proteins, with a potential clinical use recommending more aggressive management in those who are positive.In countries where cytology is of good quality, the most attractive option for primary screening is to use HPV DNA testing as the sole screening modality with cytology reserved for triage of HPV-positive women. Established cytology-based programmes should also be gradually moving towards a greater use of HPV DNA testing to improve their efficacy and safely lengthen the screening interval. The greater sensitivity of HPV DNA testing compared to cytology argues strongly for using HPV DNA testing as the primary screening test in newly implemented programmes, except where resources are extremely limited and only programmes based on visual inspection are affordable. In such countries, use of a simple HPV DNA test followed by immediate ‘screen and treat’ algorithms based on visual inspection in those who are HPV-positive are needed to minimise the number of visits and make best use of limited resources. A review of studies for visual inspection methods is presented.The fact that HPV is a sexually transmitted infection may lead to anxiety and concerns about sexual relationships. These psychosocial aspects and the need for more information and educational programmes about HPV are also discussed in this article.

Editorial

Editorial

Smear Tactics

INTRODUCTION: Cervical cancer holds significant social and financial implications not only on Irish society, but across the globe, as it is the fourth most common cancer affecting women worldwide (IARC). This project identified the incidence, presentation, time to diagnosis and association of risk factors with cervical cancer in women referred to colposcopy in Dublin, Ireland over the last 6 years. Special attention was given to analysis of women presenting to colposcopy with initial low-grade smears as recent literature has advocated for stricter guidelines referring only those women presenting with high-grade smears to colposcopy. METHODS: A retrospective study (n=148) spanning 1/1/2009–3/15/15 was conducted in the colposcopy clinic of Tallaght Hospital, serving Dublin, Ireland. Statistical analyses utilized SPSS (22.0). RESULTS: The median time to identification of cervical cancer in women presenting with abnormal smears is 64.5 days. It was found 23.6% of patients presenting with low-grade smears had cervical cancer. More women using contraceptives were found to have adenocarcinoma than squamous cell carcinoma. Associations between squamous cell carcinoma and high parity, smoking and abnormal bleeding were also observed. CONCLUSION: Nearly 24% of women presenting with initial low-grade cytology developed cervical cancer. Early treatment of these cases resulted in over €7,000,000 saved, strengthening the argument against recent European and American proposals to enforce stricter guidelines allowing only women with severe or high-grade abnormalities to be referred to colposcopy clinics. Instead, evidence put forth in this study indicates that a referral to colposcopy following a low-grade smear is indeed an appropriate clinical action with immense economic benefits.

Evidence Supporting See-and-Treat Management of Cervical Intraepithelial Neoplasia

BACKGROUND: Studies of see-and-treat management of cervical intraepithelial neoplasia (CIN) vary in their inclusion criteria, resulting in a broad range of overtreatment rates. OBJECTIVES: To determine overtreatment rates in see-and-treat management of women referred for colposcopy because of suspected CIN, in order to define circumstances supporting see-and-treat management. SEARCH STRATEGY: MEDLINE, EMBASE, and the Cochrane Library were searched from inception up to 12 May 2014. SELECTION CRITERIA: Studies of see-and-treat management in women with a reported cervical smear result, colposcopic impression, and histology result were included. DATA COLLECTION AND ANALYSIS: Methodological quality was assessed with the Newcastle-Ottawa scale. We used the inverse variance method for pooling incidences, and a random-effects model was used to account for heterogeneity between studies. Overtreatment was defined as treatment in patients with no CIN or CIN1. MAIN RESULTS: Thirteen studies (n = 4611) were included. The overall overtreatment rate in women with a high-grade cervical smear and a high-grade colposcopic impression was 11.6% (95% CI 7.8-15.3%). The overtreatment rate in women with a high-grade cervical smear and low-grade colposcopic impression was 29.3% (95% CI 16.7-41.9%), and in the case of a low-grade smear and high-grade colposcopic impression it was 46.4% (95% CI 15.7-77.1%). In women with a low-grade smear and low-grade colposcopic impression, the overtreatment rate was 72.9% (95% CI 68.1-77.7%). AUTHOR'S CONCLUSIONS: The pooled overtreatment rate in women with a high-grade smear and high-grade colposcopic impression is at least comparable with the two-step procedure, which supports the use of see-and-treat management in this subgroup of women. TWEETABLE ABSTRACT: See-and-treat management is justified in the case of a high-grade smear and a high-grade colposcopic impression.

See-and-treat: striking a balance between over- and under-treatment.

Secondary prevention of cervical cancer based on cervical cytology generally employs a multi-visit approach: screening with cytology, diagnosis with colposcopically directed biopsy, and treatment. Updated screening and management guidelines emphasise the precision of diagnosis and use estimates of risk to avoid overtreatment or undertreatment. The need to return for multiple visits presents an obstacle for many women and may prevent them from completing the process from screening to treatment. A recent analysis of a population-based screening registry in New Mexico found that 16.3% of women with cervical smear tests indicating high-grade squamous intraepithelial lesions had no follow up within a 12-month period. Those with low-grade smears had higher rates of loss to follow up. Furthermore, among those with a high-grade smear who had a biopsy confirming cervical intraepithelial neoplasia (CIN) 3 or worse, only 60.0% received excisional treatment within 1 year (Kinney et al. Gynecol Oncol 2014;132:628–35). The see-and-treat approach can reduce loss to follow up between biopsy and treatment. Women with abnormal cytology are examined colposcopically and treated with an outpatient loop electrosurgical excision procedure in a single visit, so bypassing a visit for biopsy. There is tension between the multivisit approach with its inherent risk of undertreatment from loss to follow up and see-and-treat, in which the lack of a colposcopically directed biopsy often leads to overtreatment. Overtreatment may take two forms, treatment of a cervix with less than final histology results of no CIN or CIN1, and treatment of high-grade squamous intraepithelial lesions that, if observed over time would have spontaneously regressed. Ebisch et al. in this issue of BJOG analyse the impact of cytology and colposcopic impression on overtreatment, i.e. ultimate histology of no CIN or CIN1 (BJOG 2015;doi: 10.1111/1471-0528.13530). They extracted data from 13 studies and show a relatively low (11.6%) rate of overtreatment in women with both high-grade cytology and a high-grade colposcopic impression. The overtreatment rate in this group of women was significantly lower than in those with high-grade cytology and a low-grade colposcopic impression (29.3%) or those with low-grade smear regardless of whether the colposcopic impression was high-grade (46.4%) or low-grade (72.9%). The management guidelines of the American Society for Colposcopy and Cervical Pathology (ASCCP) recommend see-and-treat as an acceptable option in cases of a high-grade smear, when possible perinatal risks from excision are not a consideration. (Massad et al. J Low Genit Tract Dis 2013;17:S1–27). Colposcopic impression is not part of the ASCCP metric, but human papillomavirus status, if known and in the rare case that it is negative, may be considered. Ebisch's data suggest that colposcopic impression may indeed have a role to play when a high-grade smear is associated with a low-grade colposcopic impression. In these women, as part of shared decision-making, biopsy may be the better option. Clearly see-and-treat is an important option in selected women; it can reduce incomplete care. Can we further reduce overtreatment? Additional research is needed to evaluate the possible role of biomarkers such as human papillomavirus genotypes or immunostains, or newer imaging modalities. More and larger studies evaluating the role of the colposcopic impression are also needed. Full disclosure of interests available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Evidence supporting see‐and‐treat management of cervical intraepithelial neoplasia: a systematic review and meta‐analysis

Studies of see-and-treat management of cervical intraepithelial neoplasia (CIN) vary in their inclusion criteria, resulting in a broad range of overtreatment rates. To determine overtreatment rates in see-and-treat management of women referred for colposcopy because of suspected CIN, in order to define circumstances supporting see-and-treat management. MEDLINE, EMBASE, and the Cochrane Library were searched from inception up to 12May2014. Studies of see-and-treat management in women with a reported cervical smear result, colposcopic impression, and histology result were included. Methodological quality was assessed with the Newcastle-Ottawa scale. We used the inverse variance method for pooling incidences, and a random-effects model was used to account for heterogeneity between studies. Overtreatment was defined as treatment in patients with no CIN or CIN1. Thirteen studies (n=4611) were included. The overall overtreatment rate in women with a high-grade cervical smear and a high-grade colposcopic impression was 11.6% (95%CI 7.8-15.3%). The overtreatment rate in women with a high-grade cervical smear and low-grade colposcopic impression was 29.3% (95%CI 16.7-41.9%), and in the case of a low-grade smear and high-grade colposcopic impression it was 46.4% (95%CI 15.7-77.1%). In women with a low-grade smear and low-grade colposcopic impression, the overtreatment rate was 72.9% (95%CI 68.1-77.7%). The pooled overtreatment rate in women with a high-grade smear and high-grade colposcopic impression is at least comparable with the two-step procedure, which supports the use of see-and-treat management in this subgroup of women. See-and-treat management is justified in the case of a high-grade smear and a high-grade colposcopic impression.

Overtreatment in a See-and-Treat Approach to Cervical Intraepithelial Lesions

To determine the overtreatment rate at colposcopy in women who underwent a see-and-treat protocol. We identified 3,192 patients (mean age 36 years, standard deviation 8.7) who underwent a see-and-treat protocol in Radboud University Nijmegen Medical Center between January 1981 and December 2010. Overtreatment, defined as cervical intraepithelial neoplasia 1 or less at final histopathology analysis, was investigated in relation to the age of the women, time of referral, cervical smear result, colposcopic impression, and histopathology result. A total of 579 women (18.1%, 95% confidence interval [CI] 16.7-19.5) were overtreated. The lowest overtreatment rate (4.5%, 95% CI 3.5-5.5) was seen in women with both a high-grade cervical smear result and a high-grade colposcopic impression. Women aged younger than 40 years were less likely to be overtreated (13.1%, 95% CI 11.7-14.5) than women aged 40-49 years (24.2% 95% CI 21.2-27.4, number needed to harm nine) and aged 50 years and older (42.2%, 95% CI 36.5-47.7, number needed to harm three). The overtreatment rate is low for patients with both a high-grade smear result and a high-grade colposcopic impression, justifying a see-and-treat approach for these patients. In women with either a high-grade smear result or a high-grade impression on colposcopy, a see-and-treat approach may still be preferable but has higher overtreatment rates. Given the side effects of cervical surgery on pregnancy outcome, young women, in particular those who have either a low-grade smear result or low-grade impression on colposcopy, are better served by a two-step approach. In older women, a see-and-treat policy may be preferable.

Does Experience in Colposcopy Improve Identification of High Grade Abnormalities?

Abstract Objective This study investigates whether experience in colposcopy improves identification of high grade abnormalities. The sensitivity and positive predictive value (PPV) of colposcopy in identifying high grade intra-epithelial lesions (HSIL) performed by relatively inexperienced as compared to experienced colposcopists are evaluated. Study design Of 18,421 colposcopies performed at the Royal Women's Hospital, Melbourne, Australia, between 1999 and 2004 by 5 senior and 11 junior colposcopists, the colposcopic impression was correlated with the histopathology result of the biopsy taken at 6020 colposcopies, with respect to the experience of the colposcopist. Results Colposcopy had a 60% sensitivity and 60% PPV in identifying HSIL in this study. In case of a high-grade referral smear the sensitivity and PPV in identifying HSIL were, respectively 76% and 73%, compared with 26% and 48% in case of a low-grade referral smear, no difference in overall colposcopic performance between experienced and inexperienced colposcopists was observed. However, the sensitivity of identifying HSIL was significantly higher with inexperienced colposcopists, and the PPV was significantly higher with experienced colposcopists. Conclusion In this study experience did not improve colposcopic performance, but differences in colposcopic strategy between the two groups were noted. The rather low overall sensitivity and PPV of colposcopy in identifying HSIL, especially in case of a low-grade referral smear, indicate that the role of colposcopy in the detection and treatment of cervical abnormalities is to assess size, site, and extent of an abnormality, rather than to assess the severity of this abnormality. Histology must remain the gold standard for treatment.

Characterising the local immune responses in cervical intraepithelial neoplasia: a cross‐sectional and longitudinal analysis

Immunological competence influences the progression of cervical intraepithelial neoplasia (CIN) to invasive cancer. Information on the local immunological changes during the natural course of CIN is central for the development of new therapies. This study defines the populations of tissue-infiltrating immune cells in a cross-sectional cohort of different grades of CIN and also in a longitudinal cohort of regressing, persistent and progressing low-grade (LG)-CIN. A cohort of 125 women with LG cytological atypia was recruited, of which 64/125 (51%) women with LG-CIN were followed prospectively for 1 year. Paraffin-embedded entry and exit cervical biopsies were used for immunohistochemistry analysis (CD4, CD8, CD56, FOXP3, CD1a and granzyme B). At recruitment, 74/125 (59%), 39/125 (31%) and 12/125 (10%) women referred with LG smears had histologically proven LG-CIN, high-grade (HG) and normal biopsies, respectively. Seventeen of 64 (24.6%) women with LG-CIN progressed to HG-CIN within 1 year. In both LG-CIN and HG-CIN, the predominant intraepithelial cell population were cytotoxic T cells, while CD4+ and FOXP3+ T cells predominated the stromal compartment. Women with LG-CIN who later on regressed displayed a significantly higher number of cytotoxic (granzyme B+) cells in their entry samples. In addition, the ratio between CD8+ cells and granzyme B+ cells was close to 1, suggesting that all infiltrating CD8+ T cells were highly active. In contrast, this ratio was three-fold lower in women, in whom the lesions persisted or progressed. This study suggests that the early infiltration of lesions by highly cytotoxic effector cells protects against progression.

Overview of Human Papillomavirus-Based and Other Novel Options for Cervical Cancer Screening in Developed and Developing Countries

Screening for cervical cancer precursors by cytology has been very successful in countries where adequate resources exist to ensure high quality and good coverage of the population at risk. Mortality reductions in excess of 50% have been achieved in many developed countries; however the procedure is generally inefficient and unworkable in many parts of the world where the appropriate infrastructure is not achievable. A summary and update of recently published meta-analyses and systematic reviews on four possible clinical applications of human papillomavirus (HPV) DNA testing is provided in this article: (1) triage of women with equivocal or low-grade cytological abnormalities; (2) follow-up of women with abnormal screening results who are negative at colposcopy/biopsy; (3) prediction of the therapeutic outcome after treatment of cervical intraepithelial neoplasia (CIN), and most importantly (4) primary screening HPV DNA test, solely or in combination with Pap smear to detect cervical cancer precursors. There are clear benefits for the use of HPV DNA testing in the triage of equivocal smears, low-grade smears in older women and in the post-treatment surveillance of women after treatment for CIN. However, there are still issues regarding how best to use HPV DNA testing in primary screening. Primary screening with Hybrid Capture ® 2 (HC2) generally detects more than 90% of all CIN2, CIN3 or cancer cases, and is 25% (95% CI): 15–36%) relatively more sensitive than cytology at a cut-off of abnormal squamous cells of undetermined significance (ASC-US) (or low-grade squamous intraepithelial lesions (LSIL) if ASC-US unavailable), but is 6% (95% CI: 4–7%) relatively less specific. Several approaches are currently under evaluation to deal with the lower specificity of HPV DNA testing as associated with transient infection. These include HPV typing for HPV-16 and -18/45, markers of proliferative lesions such as p16 and mRNA coding for the viral E6 and/or E7 proteins, with a potential clinical use recommending more aggressive management in those who are positive. In countries where cytology is of good quality, the most attractive option for primary screening is to use HPV DNA testing as the sole screening modality with cytology reserved for triage of HPV-positive women. Established cytology-based programmes should also be gradually moving towards a greater use of HPV DNA testing to improve their efficacy and safely lengthen the screening interval. The greater sensitivity of HPV DNA testing compared to cytology argues strongly for using HPV DNA testing as the primary screening test in newly implemented programmes, except where resources are extremely limited and only programmes based on visual inspection are affordable. In such countries, use of a simple HPV DNA test followed by immediate ‘screen and treat’ algorithms based on visual inspection in those who are HPV-positive are needed to minimise the number of visits and make best use of limited resources. A review of studies for visual inspection methods is presented. The fact that HPV is a sexually transmitted infection may lead to anxiety and concerns about sexual relationships. These psychosocial aspects and the need for more information and educational programmes about HPV are also discussed in this article.

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.

A long‐term study of women with normal colposcopy after referral with low‐grade cytological abnormalities

Background About 50 000 women are referred annually to colposcopy in England because of a low-grade smear. About 35% of these women have no colposcopic abnormality but are followed up in the colposcopy clinic because of uncertainty about the risk of significant pathology. Objective This study determined the 5-year rate of disease when initial colposcopy was normal and smear was non-dyskaryotic. Design Retrospective study. Setting Colposcopy clinic of an inner city postgraduate teaching hospital. Population Two thousand one hundred and fifty seven women referred between January 1990 and December 2001 with mild dyskaryosis (Low Grade Squamous Intraepithelial Lesion [LSIL]) or borderline nuclear changes (Abnormal Squamous Changes of Uncertain Significance [ASCUS]). Methods Information was obtained from the colposcopy clinic database and Open-Exeter. Time plots of the disease-free rates were generated using the Kaplan–Meier method, and statistical comparisons were performed using Cox regression. Main outcome measures Cumulative rates of cytological and histological abnormalities. Results High-grade or invasive disease was diagnosed histologically in 12.8% of 805 women referred with borderline nuclear changes and in 35.8% of 1352 referred with mild dyskaryosis. Among 620 women with normal colposcopy and a negative or borderline repeat smear, high-grade disease was found after 5 years of follow up in 1.3% of women originally referred with a borderline smear and in 8.5% referred because of mild dyskaryosis. Conclusion Women referred to colposcopy with borderline nuclear changes or mild dyskaryosis whose colposcopy findings are normal and whose repeat smear in the clinic is non-dyskaryotic may be discharged for routine 3-yearly screening in the community because the risk of high-grade disease in the next 5 years is small.

Is it rational to start population-based cervical cancer screening at or soon after age 20? Analysis of time trends in preinvasive and invasive diseases

The effect of starting screening at age 20 in 1988 was assessed by analysing (a) the age-specific incidence and distribution of stage and histology of invasive diseases, and (b) the detection rates of histologic moderate to high-grade intraepithelial neoplasia (CIN 2–3/AIS), and 1st abnormal cytology and repeat low-grade cytology after follow-up observation. Cancer incidence increased significantly at age 25–34 after 1979 due to early stage squamous cell and adenocarcinoma. After an initial increased rate of preinvasive disease, CIN 3 decreased significantly at age 30–34 after 1988, at age 25–29 after 1993, and levelled out after 1998 at age 20–24. The rates of CIN 2 levelled out after 1998. The rates of repeat low-grade smears decreased after observation at age 20–24 by 80%. The study confirms an increasing rate of preinvasive and invasive disease among younger women and indicates the benefit of starting organised screening at 2–3 year intervals soon after age 20.

A long‐term study of women with normal colposcopy after referral with low‐grade cytological abnormalities

About 50,000 women are referred annually to colposcopy in England because of a low-grade smear. About 35% of these women have no colposcopic abnormality but are followed up in the colposcopy clinic because of uncertainty about the risk of significant pathology. This study determined the 5-year rate of disease when initial colposcopy was normal and smear was non-dyskaryotic. Retrospective study. Colposcopy clinic of an inner city postgraduate teaching hospital. Population Two thousand one hundred and fifty seven women referred between January 1990 and December 2001 with mild dyskaryosis (Low Grade Squamous Intraepithelial Lesion [LSIL]) or borderline nuclear changes (Abnormal Squamous Changes of Uncertain Significance [ASCUS]). Information was obtained from the colposcopy clinic database and Open-Exeter. Time plots of the disease-free rates were generated using the Kaplan-Meier method, and statistical comparisons were performed using Cox regression. Cumulative rates of cytological and histological abnormalities. High-grade or invasive disease was diagnosed histologically in 12.8% of 805 women referred with borderline nuclear changes and in 35.8% of 1352 referred with mild dyskaryosis. Among 620 women with normal colposcopy and a negative or borderline repeat smear, high-grade disease was found after 5 years of follow up in 1.3% of women originally referred with a borderline smear and in 8.5% referred because of mild dyskaryosis. Women referred to colposcopy with borderline nuclear changes or mild dyskaryosis whose colposcopy findings are normal and whose repeat smear in the clinic is non-dyskaryotic may be discharged for routine 3-yearly screening in the community because the risk of high-grade disease in the next 5 years is small.

Low-Grade Pap Smears Containing Occasional High-Grade Cells as a Predictor of High-Grade Dysplasia

ObjectivesThis study compared clinical outcomes associated with Pap smear reports of atypical squamous cells cannot exclude HSIL (ASC-H) and those associated with “low-grade smears containing occasional cells suggestive of HSIL” (LSIL-H). In Alberta, women with ASC-H are referred for colposcopy, and women with LSIL are managed with follow-up Pap smears. LSIL-H is not included in the Bethesda classification and has not been characterized in terms of cytological features, reporting, management, and clinical course. MethodsAll ASC-H (n = 153) and LSIL-H (n = 189) Pap smears recorded in the regional laboratory information system between December 2000 and December 2001 were identified. All available histology for each associated patient over the subsequent two-year period was reviewed to determine if a high-grade histological lesion was ever confirmed in a biopsy, loop electrosurgical excision procedure (LEEP), or hysterectomy specimen. ResultsA high-grade squamous intraepithelial lesion was identified in 48% of the ASC-H group and 40% of the LSIL-H group (P = 0.136). Most of the HSIL histopathology was identified on the first colposcopic visit, suggesting that high-grade dysplasia may have been present at the time of the original Pap smear. ConclusionsPap smears reporting ASC-H and LSIL-H predict a high-grade squamous intraepithelial lesion with similar accuracy. Since approximately 40% of patients with an LSIL-H Pap smear have either concurrent or subsequent high-grade cervical pathology, we also recommend immediate referral for colposcopy in this group of patients.

Longitudinal trends in cervical cytological lesions and the effect of risk factors. A 30‐year overview

Cytological preinvasive changes are important precursors in cervical cancer, therefore variations in their trends affect screening guidelines. Trends in cytological preinvasive changes following the 1st to 5th screening visits in the 20-34 and 35-69 year age groups were analyzed for the period 1979-2002: a) the incidence rate (absolute risk) of higher grade cytology and the relative risk of risk factors on this rate; b) the cumulative incidence of low-grade and higher grade smears after normal and abnormal screening results; c) the cumulative incidence of higher grade cytology at a fixed risk level after normal screening results; and d) the prevalence of higher grade smears at first screening visit in the 20-24/25-29 year age groups during 1971-2002. An increased trend in the prevalence of higher-grade smears was observed at the first screening visit after 1980. The main risk variables for higher-grade smears in both age groups were low-grade changes and inflammation followed in the younger age group by calendar year. However, age correlated with a decreased risk ratio. After normal screening the cumulative incidence rate of low and higher-grade smears increased almost linearly with time. The screening interval before diagnosis of higher-grade smears increased with both age and number of normal visits, but leveled out after the age of 35-40. Trends in higher-grade smears indicate that screening should preferably start before age 25 with a maximum interval of 3 years. The interval can be extended after age 35-40. Low-grade smears or inflammation need closer follow-up.