European Federation for Colposcopy and Institut national du Cancer (INCA).

ObjectiveTo estimate the regression, persistence, and progression of untreated cervical intraepithelial neoplasia grade 2 (CIN2) lesions managed conservatively as well as compliance with follow-up protocols.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1 January 1973 to 20 August 2016.Eligibility criteriaStudies reporting on outcomes of histologically confirmed CIN2 in non-pregnant women, managed conservatively for three or more months.Data synthesisTwo reviewers extracted data and assessed risk of bias. Random effects model was used to calculate pooled proportions for each outcome, and heterogeneity was assessed using I2 statistics.Main outcome measuresRates of regression, persistence, or progression of CIN2 and default rates at different follow-up time points (3, 6, 12, 24, 36, and 60 months).Results36 studies that included 3160 women were identified (seven randomised trials, 16 prospective cohorts, and 13 retrospective cohorts; 50% of the studies were at low risk of bias). At 24 months, the pooled rates were 50% (11 studies, 819/1470 women, 95% confidence interval 43% to 57%; I2=77%) for regression, 32% (eight studies, 334/1257 women, 23% to 42%; I2=82%) for persistence, and 18% (nine studies, 282/1445 women, 11% to 27%; I2=90%) for progression. In a subgroup analysis including 1069 women aged less than 30 years, the rates were 60% (four studies, 638/1069 women, 57% to 63%; I2=0%), 23% (two studies, 226/938 women, 20% to 26%; I2=97%), and 11% (three studies, 163/1033 women, 5% to 19%; I2=67%), respectively. The rate of non-compliance (at six to 24 months of follow-up) in prospective studies was around 10%.ConclusionsMost CIN2 lesions, particularly in young women (<30 years), regress spontaneously. Active surveillance, rather than immediate intervention, is therefore justified, especially among young women who are likely to adhere to monitoring.Systematic review registrationPROSPERO 2014: CRD42014014406.

Primary HPV DNA screening with cytology triage is more sensitive than conventional screening. Among women aged 35 years or older, primary HPV DNA screening with cytology triage is also more specific than conventional screening and decreases colposcopy referrals and follow-up tests.

Background: Attendance in screening is an important determinant of cervical cancer. Previous experience on high-risk human papillomavirus (hrHPV) DNA testing on patient-obtained samples suggests a good effect among nonattendees of screening. We assessed the effects of self-sampling on attendance in the Finnish screening program.Methods: Nonattendees after the primary invitation in one municipality (Espoo) were randomized to receive either a self-sampling kit (2,397 women) or an extra invitation (6,302 women). One fourth (1,315 women) of reminder letter arm nonattendees also received a self-sampling kit as a third intervention. Main outcomes were increases in screening attendance and coverage.Results: The adjusted relative risk for participation by self-sampling as a second intervention in comparison to a reminder letter arm was 1.21 (95% CI: 1.13-1.30). Total attendance increased from 65% to 76% by selfsampling and from 65% to 74% with a reminder letter. Combining the interventions (reminder letter and then self-sampling) increased total attendance from 63% to 78%. One fifth of the participants in all three groups increased screening coverage (previous Pap smear !5 years ago or never). Self-obtained samples were more often HPV positive than provider-obtained ones (participants after primary invitation and reminder letter), 12% to 13% versus 7%.Conclusions: Self-sampling is a feasible option in enhancing the attendance at organized screening, particularly as an addition to a reminder letter.Impact: If self-sampling is used as a third intervention after two written invitations, the overall attendance in Finland could most likely reach the desired 80% to 85%. Cancer Epidemiol Biomarkers Prev; 20(9); 1960-9. Ó2011 AACR.

Objective To assess the performance and impact of primary human papillomavirus (HPV) DNA screening with cytology triage compared with conventional cytology on cervical cancer and severe pre-cancerous lesions. Design Randomised trial. Setting Population based screening programme for cervical cancer in southern Finland in 2003-5. Participants 58 076 women, aged 30-60, invited to the routine population based screening programme for cervical cancer. Interventions Primary HPV DNA test (hybrid capture II) with cytology triage if the result was positive or conventional cytological screening (reference). Main outcome measures Rate of cervical cancer, cervical intraepithelial neoplasia (CIN) grade III, and adenocarcinoma in situ (as a composite outcome referred to as CIN III+) during 2003-7 through record linkage between files from the screening registry and the national cancer registry. Results In the HPV and conventional arms there were 95 600 and 95 700 woman years of follow-up and 76 and 53 cases of CIN III+, respectively (of which six and eight were cervical cancers). The relative rate of CIN III+ in the HPV arm versus the conventional arm was 1.44 (95% confidence interval 1.01 to 2.05) among all women invited for screening and 1.77 (1.16 to 2.74) among those who attended. Among women with a normal or negative test result, the relative rate of subsequent CIN III+ was 0.28 (0.04 to 1.17). The rate of cervical cancer between arms was 0.75 (0.25 to 2.16) among women invited for screening and 1.98 (0.52 to 9.38) among those who attended. Conclusions When incorporated into a well established organised screening programme, primary HPV screening with cytology triage was more sensitive than conventional cytology in detecting CIN III+ lesions. The number of cases of cervical cancer was small, but considering the high probability of progression of CIN III the findings are of importance regarding cancer prevention.Trial registration Current Controlled Trials ISRCTN23885553.

European guidelines for quality assurance in cervical cancer screening: recommendations for clinical management of abnormal cervical cytology, part 1The current paper presents the first part of Chapter 6 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. It provides guidance on how to manage women with abnormal cervical cytology. Throughout this article the Bethesda system is used for cervical cytology terminology, as the European guidelines have recommended that all systems should at least be translated into that terminology while cervical intraepithelial neoplasia (CIN) is used for histological biopsies (Cytopathology 2007; 18:213-9). A woman with a high-grade cytological lesion, a repeated low-grade lesion or with an equivocal cytology result and a positive human papillomavirus (HPV) test should be referred for colposcopy. The role of the colposcopist is to identify the source of the abnormal cells and to make an informed decision as to whether or not any treatment is required. If a patient requires treatment the colposcopist will decide which is the most appropriate method of treatment for each individual woman. The colposcopist should also organize appropriate follow-up for each woman seen. Reflex testing for high-risk HPV types of women with atypical squamous cells (ASC) of undetermined significance with referral for colposcopy of women who test positive is a first option. Repeat cytology is a second possibility. Direct referral to a gynaecologist should be restricted to special circumstances. Follow-up of low-grade squamous intraepithelial lesion is more difficult because currently there is no evidence to support any method of management as being optimal; repeat cytology and colposcopy are options, but HPV testing is not sufficiently selective, unless for older women. Women with high-grade squamous intraepithelial lesion (HSIL) or atypical squamous cells, cannot exclude HSIL (ASC-H) should be referred without triage. Women with glandular lesions require particular attention. In a subsequent issue of Cytopathology, the second part of Chapter 6 will be presented, with recommendations for management and treatment of histologically confirmed intraepithelial neoplasia and guidance for follow-up of special cases such as women who are pregnant, postmenopausal or immunocompromised.

Objective To study the long term risk of cervical and other cancers after treatment for cervical intraepithelial neoplasia. Design Retrospective cohort study. Setting University Hospital, Helsinki, Finland. Participants 7564 women treated for cervical intraepithelial neoplasia during 1974 and 2001 and followed up through the Finnish cancer registry until 2003. Main outcome measures Standardised incidence ratio for cervical cancer and other cancers.Results During follow-up 22 cases of invasive cervical cancer occurred in women treated for cervical intraepithelial neoplasia (standardised incidence ratio 2.8, 95% confidence interval 1.7 to 4.2). The highest risk was during the second decade (10 cases observed: 3.1, 1.5 to 5.7). The standardised incidence ratio for cervical intraepithelial cancer type 1 was 3.1 (1.4 to 6.2) and for type 2 was 3.7 (0.9 to 10.7). Conclusions The risk of cervical cancer in the first 20 years after treatment for cervical intraepithelial neoplasia is higher than in the average population. The risk of smoking related cancers is also increased.

The Finnish mass screening program has been effective and its continuation is of utmost importance. In the future more attention should be given to glandular cell atypias in cervical smears. Thus, it might be possible to decrease the incidence of cervical adenocarcinoma.