Pregnancy incidence and outcome before and after cervical intraepithelial neoplasia: a retrospective cohort study

We performed a retrospective cohort study of 3530 women treated for cervical intraepithelial neoplasia (CIN) in Helsinki University Central Hospital, Finland, to investigate whether CIN treatment itself affects pregnancy incidence and outcome. We estimated the incidence of live births, miscarriages, extrauterine pregnancies, molar pregnancies, and termination of pregnancies (TOPs) before and after CIN treatment using nationwide registers. Women were followed up until death, emigration, sterilization, or the end of 2004. The comparison of incidence of pregnancy outcomes before and after the treatment was estimated by calculating hazard ratios (HRs) with conditional Poisson regression. After 76,162 woman-years of follow-up, the incidence of any pregnancy remained constant over CIN-treatment, HR 1.02 and 95% confidence interval (CI) 0.97-1.08, but the incidence of the first pregnancy was significantly elevated after treatment, HR 1.13, and 95% CI 1.03-1.23. The incidence of live births was significantly elevated after treatment, HR 1.08 and 95% CI 1.01-1.15. Incidence of miscarriages, TOPs, extrauterine pregnancies, and molar pregnancies was not elevated. TOPs was significantly increased in the first pregnancy, HR 1.40, 95% CI 1.15-1.72 and after treatment by the loop electrosurgical excision procedure (LEEP), HR 1.36, 95% CI 1.15-1.60. CIN treatment did not reduce pregnancy incidence and women had more live births after than before CIN treatment. TOPs was more common in the first pregnancy or after treatment by LEEP. We encourage research on the psychosocial consequences of CIN treatment also in other countries and settings

Letter to the editor on Body mass index and 20-specific cancers-re-analyses of dose-response meta-analyses of observational studies

Peer reviewe

Serum antibody response to Chlamydia trachomatis TroA and HtrA in women with tubal factor infertility

Persistent genital chlamydial infection may lead to tubal factor infertility (TFI). Chlamydia trachomatis TroA and HtrA are proteins expressed during persistent chlamydial infection in vitro. We studied serum IgG antibody response against these proteins by EIA in women with TFI and in subfertile women without tubal pathology. Altogether, 22 of 258 subfertile women (8.5%) had TFI which was unilateral in 17 cases and bilateral in 5 cases. Overall, 55 (21.3%) of the 258 women had TroA and 39 (15.1%) had HtrA antibodies. Seropositivity to TroA and HtrA was more common among women with TFI than women with other causes for subfertility (45.5 vs. 19.1%, p = 0.004 for TroA; 36.4 vs. 13.1%, p = 0.004 for HtrA). Mean absorbance values and the prevalence of TroA and HtrA antibodies increased with increasing severity of TFI. On the basis of our results, TroA and HtrA serology has the potential to be further developed to a specific biomarker for C. trachomatis-related TFI.Peer reviewe

Age-specific HPV type distribution in high-grade cervical disease in screened and unvaccinated women

Background and aim. Age-specific type-distribution of high-risk human papillomavirus (hrHPV) in cervical precancerous lesions is subject to change in the HPV vaccination era. Knowing the pre-vaccination type distribution helps to anticipate changes induced by mass vaccination and optimize screening.Methods. We recruited 1279 women referred to colposcopy for abnormal cytology into a population-based study on HPV type distribution in diagnostic cervical samples (ISRCTN10933736). The HPV genotyping findings were grouped as: HPV16/18+, other hrHPV+ (HPV31/33/35/39/45/51/52/56/58/59/66/68), non-vaccine targeted hrHPV+ (HPV35/39/51/56/59/66/68), low-risk HPV, and HPV negative. We estimated the HPV group-specific prevalence rates according to diagnostic histopathological findings in the age groups of = 45 (n = 326).Results. Altogether 503 cases with high grade squamous intraepithelial lesion or worse (HSIL+) were diagnosed. More than half, 285 (56.7%) of HSIL+ cases were associated with HPV16/18: 64.3% (101/157) in women = 45 years of age (RR 0.55, 95% CI 039-0.75). Conversely, other hrHPV's were associated with 191 (38.0%) of HSIL+: 31.9% (50/157) in women = 45 (RR 1.71, 95% CI 126-2.33). The proportion of non-vaccine targeted hrHPV and HPV negative HSIL+ increased with advancing age.Conclusions. Pre-vaccination HPV type distribution in HSIL+ was distinctly polarised by age with HPV16/18 attributed disease being markedly more prevalent in women aged <30. In the older women the other hrHPV types, however, dominated suggesting a need for more age-dependent screening strategies. (C) 2019 The Authors. Published by Elsevier Inc

Incidence and mortality from cervical cancer and other malignancies after treatment of cervical intraepithelial neoplasia: a systematic review and meta-analysis of the literature

Background Although local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical and other cancers. Our aim is to explore the risk of developing or dying from cervical cancer and other human papillomavirus (HPV)- and non-HPV-related malignancies after CIN treatment and infer its magnitude compared with the general population. Materials and methods Design: Systematic review and meta-analysis. Eligibility criteria: Studies with registry-based follow-up reporting cancer incidence or mortality after CIN treatment. Data synthesis: Summary effects were estimated using random-effects models. Outcomes Incidence rate of cervical cancer among women treated for CIN (per 100 000 woman-years). Relative risk (RR) of cervical cancer, other HPV-related anogenital tract cancer (vagina, vulva, anus), any cancer, and mortality, for women treated for CIN versus the general population. Results Twenty-seven studies were eligible. The incidence rate for cervical cancer after CIN treatment was 39 per 100 000 woman-years (95% confidence interval 22–69). The RR of cervical cancer was elevated compared with the general population (3.30, 2.57–4.24; P <0.001). The RR was higher for women more than 50 years old and remained elevated for at least 20 years after treatment. The RR of vaginal (10.84, 5.58–21.10; P <0.001), vulvar (3.34, 2.39–4.67; P <0.001), and anal cancer (5.11, 2.73–9.55; P <0.001) was also higher. Mortality from cervical/vaginal cancer was elevated, but our estimate was more uncertain (RR 5.04, 0.69–36.94; P = 0.073). Conclusions Women treated for CIN have a considerably higher risk to be later diagnosed with cervical and other HPV-related cancers compared with the general population. The higher risk of cervical cancer lasts for at least 20 years after treatment and is higher for women more than 50 years of age. Prolonged follow-up beyond the last screening round may be warranted for previously treated women.Peer reviewe

Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance : systematic review and meta-analysis

OBJECTIVE To 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. DESIGN Systematic review and meta-analysis. DATA SOURCES Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1 January 1973 to 20 August 2016. ELIGIBILITY CRITERIA Studies reporting on outcomes of histologically confirmed CIN2 in non-pregnant women, managed conservatively for three or more months. DATA SYNTHESIS Two 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 I-2 statistics. MAIN OUTCOME MEASURES Rates of regression, persistence, or progression of CIN2 and default rates at different follow-up time points (3, 6, 12, 24, 36, and 60 months). RESULTS 36 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%; I-2= 77%) for regression, 32% (eight studies, 334/1257 women, 23% to 42%; I-2= 82%) for persistence, and 18% (nine studies, 282/1445 women, 11% to 27%; I-2= 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%; I-2= 0%), 23% (two studies, 226/938 women, 20% to 26%; I-2= 97%), and 11% (three studies, 163/1033 women, 5% to 19%; I-2= 67%), respectively. The rate of non-compliance (at six to 24 months of follow-up) in prospective studies was around 10%. CONCLUSIONS Most 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.Peer reviewe

The intelligent-Knife (i-Knife) and its intraoperative diagnostic advantage for the treatment of cervical disease

Clearance of surgical margins in cervical cancer prevents the need for adjuvant chemoradiation and allows fertility preservation. In this study, we determined the capacity of the rapid evaporative ionization mass spectrometry (REIMS), also known as intelligent knife (iKnife), to discriminate between healthy, preinvasive, and invasive cervical tissue. Cervical tissue samples were collected from women with healthy, human papilloma virus (HPV) ± cervical intraepithelial neoplasia (CIN), or cervical cancer. A handheld diathermy device generated surgical aerosol, which was transferred into a mass spectrometer for subsequent chemical analysis. Combination of principal component and linear discriminant analysis and least absolute shrinkage and selection operator was employed to study the spectral differences between groups. Significance of discriminatory m/z features was tested using univariate statistics and tandem MS performed to elucidate the structure of the significant peaks allowing separation of the two classes. We analyzed 87 samples (normal = 16, HPV ± CIN = 50, cancer = 21 patients). The iKnife discriminated with 100% accuracy normal (100%) vs. HPV ± CIN (100%) vs. cancer (100%) when compared to histology as the gold standard. When comparing normal vs. cancer samples, the accuracy was 100% with a sensitivity of 100% (95% CI 83.9 to 100) and specificity 100% (79.4 to 100). Univariate analysis revealed significant MS peaks in the cancer-to-normal separation belonging to various classes of complex lipids. The iKnife discriminates healthy from premalignant and invasive cervical lesions with high accuracy and can improve oncological outcomes and fertility preservation of women treated surgically for cervical cancer. Larger in vivo research cohorts are required to validate these findings

“After Lunch We Offer Quiet Time and Meditation” : Early Learning Environments in Australia and Finland Through the Lenses of Educators

Modern societies organize ECEC services from their own cultural, social and political contexts, which is also reflected in the steering documents of the country and further in the work of teachers (Garvis, et al., 2018). In many of the countries children’s access to preschool has broadened and the benefits of high quality ECEC have been recognized. In Australia and Finland, concepts of play based learning, child initiated play or free play have been highlighted as founding pillars of the early learning environments. In this paper we take a closer look at ECEC environments in Australia and Finland through the lenses of 26 educators. They described in an online questionnaire children’s daily activities as well as they indicated the amount of free play related to these activities.Peer reviewe

Cleidocranial dysplasia presenting with retained deciduous teeth in a 15-year-old girl: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cleidocranial dysplasia is a rare congenital defect of autosomal dominant inheritance caused by mutations in the <it>Cbfa1 </it>gene, also called <it>Runx2</it>, located on the short arm of chromosome 6. It primarily affects bones which undergo intramembranous ossification. This condition is of clinical significance to dentistry due to the involvement of the facial bones, altered eruption patterns and multiple supernumerary teeth.</p> <p>Case presentation</p> <p>Our patient, a 15-year-old Indian girl, presented with the typical features of prolonged retention of deciduous dentition and delayed eruption of permanent teeth, that is, mandibular prognathism along with other skeletal abnormalities like shrugged shoulder and the absence of clavicles. A multidisciplinary approach was followed, comprising orthodontic, surgical and pedodontic teams for management.</p> <p>Conclusion</p> <p>Successful treatment of such a case lies in a holistic approach that takes care of all aspects, including the primary pathology, the deformity itself and even the psychological angle.</p