Role of Colposcopy after Treatment for Cervical Intraepithelial Neoplasia

Colposcopy is often used in follow-up after treatment for cervical intraepithelial neoplasia (CIN) despite its marked inter-observer variability and low sensitivity. Our objective was to assess the role of colposcopy in post-treatment follow-up in comparison to hrHPV (high-risk human papillomavirus) testing, cytology, and cone margin status. Altogether, 419 women treated for histological high-grade lesion (HSIL) with large loop excision of the transformation zone (LLETZ) attended colposcopy with cytology and hrHPV test at six months. Follow-up for recurrence of HSIL continued for 24 months. Colposcopy was considered positive if colposcopic impression was recorded as high grade and cytology if HSIL, ASC-H (atypical squamous cells, cannot exclude HSIL), or AGC-FN (atypical glandular cells, favor neoplasia) were present. Overall, 10 (10/419, 2.4%) recurrent HSIL cases were detected, 5 at 6 months and 5 at 12 months. Colposcopic impression was recorded at 407/419 6-month visits and was positive for 11/407 (2.7%). None of them had recurrent lesions, resulting in 0% sensitivity and 97% specificity for colposcopy. Sensitivity for the hrHPV test at 6 months was 100% and specificity 85%, for cytology 40% and 99%, and for margin status at treatment 60% and 82%, respectively. While the hrHPV test is highly sensitive in predicting recurrence after local treatment for CIN, colposcopy in an unselected population is not useful in follow-up after treatment of CIN.Peer reviewe

Methylation in predicting progression of untreated high-grade cervical intraepithelial neoplasia

BACKGROUND: There is no baseline prognostic test to ascertain whether cervical intraepithelial neoplasia (CIN) will regress or progress. The majority of CIN regress in young women and since local treatments are known to increase the risk of adverse pregnancy outcomes interventions need to be sparing. We investigated the ability of a DNA methylation panel (the S5-classifier) to discriminate between progression and regression among women of childbearing age with untreated CIN grade 2 (CIN2). METHODS: Pyrosequencing methylation and HPV genotyping assays were performed on exfoliated cervical cells from 149 young women with CIN2 in a 2-year cohort study of active surveillance. RESULTS: Twenty-five lesions progressed to CIN grade 3 or worse, 88 regressed to less than CIN grade 1, and 36 lesions persisted as CIN1/2. When cytology, HPV16/18- and HPV16/18/31/33-genotyping, and S5 at baseline were compared to outcomes, S5 was the strongest biomarker associated with regression versus progression. S5 alone or in combination with HPV16/18/31/33-genotyping also showed significantly increased sensitivity versus cytology, comparing regression vs. persistence/progression. With both S5 and cytology tests set at a specificity of 38.6% (95% CI 28.4-49.6) the sensitivity of S5 was significantly higher (83.6%, 95% CI 71.9-91.8) than for cytology (62.3%, 95% CI 49.0-74.4) (p=0.005). The highest area under the curve (AUC) was 0.735 (95% CI 0.621-0.849) in the regression vs. progression outcome with a combination of S5 and cytology, whereas HPV16/18 or HPV16/18/31/33-genotyping did not provide additional prognostic information. CONCLUSIONS: The S5-classifier shows high potential as a prognostic biomarker to identify women with progressive CIN2.Peer reviewe

Distribution of HPV Genotypes Differs Depending on Behavioural Factors among Young Women

Risk factors for the different human papillomavirus (HPV) genotypes are not well understood, although the risk of cancer is known to vary among them. Our aim was to evaluate the association of diverse behavioral and reproductive factors with genotype-specific HPV prevalence among 879 unvaccinated women aged 18–75 years referred to the colposcopy clinic at Helsinki University Hospital in Finland. Cervical swabs for HPV genotyping were collected in the first visit and assessed for 34 high-risk (hr) and low-risk (lr) HPV genotypes. Participants completed a questionnaire on behavioral, reproductive, and lifestyle factors. Differences in genotype-specific HPV prevalence were analyzed overall and in age groups using binary logistic regression. Smoking was associated with higher prevalence in HPV16 compared with other hrHPV genotypes together with decreasing age, being highest among younger women 20 years of age, with an OR of 0.43 (95% CI 0.23–0.83). This association was not seen with other hrHPV genotypes. Methods of contraception seemed not to have an effect on hrHPV positivity, regardless of the HPV genotype. The genotype specific hrHPV prevalence differs, depending on behavioral factors, especially among younger women referred to colposcopy

Distribution of HPV Genotypes Differs Depending on Behavioural Factors among Young Women

Risk factors for the different human papillomavirus (HPV) genotypes are not well understood, although the risk of cancer is known to vary among them. Our aim was to evaluate the association of diverse behavioral and reproductive factors with genotype-specific HPV prevalence among 879 unvaccinated women aged 18–75 years referred to the colposcopy clinic at Helsinki University Hospital in Finland. Cervical swabs for HPV genotyping were collected in the first visit and assessed for 34 high-risk (hr) and low-risk (lr) HPV genotypes. Participants completed a questionnaire on behavioral, reproductive, and lifestyle factors. Differences in genotype-specific HPV prevalence were analyzed overall and in age groups using binary logistic regression. Smoking was associated with higher prevalence in HPV16 compared with other hrHPV genotypes together with decreasing age, being highest among younger women 20 years of age, with an OR of 0.43 (95% CI 0.23–0.83). This association was not seen with other hrHPV genotypes. Methods of contraception seemed not to have an effect on hrHPV positivity, regardless of the HPV genotype. The genotype specific hrHPV prevalence differs, depending on behavioral factors, especially among younger women referred to colposcopy

Overtreatment rate after immediate local excision of suspected cervical intraepithelial neoplasia: a prospective cohort study

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 agedPeer reviewe

Parastomal Hernia : A Retrospective Nationwide Cohort Study Comparing Different Techniques with Long-Term Follow-Up

Background Parastomal hernia repair is a complex surgical procedure with high recurrence and complication rates. This retrospective nationwide cohort study presents the results of different parastomal hernia repair techniques in Finland. Methods All patients who underwent a primary end ostomy parastomal hernia repair in the nine participating hospitals during 2007-2017 were included in the study. The primary outcome measure was recurrence rate. Secondary outcomes were complications and re-operation rate. Results In total, 235 primary elective parastomal hernia repairs were performed in five university hospitals and four central hospitals in Finland during 2007-2017. The major techniques used were the Sugarbaker (38.8%), keyhole (16.3%), and sandwich techniques (15.4%). In addition, a specific intra-abdominal keyhole technique with a funnel-shaped mesh was utilized in 8.3% of the techniques; other parastomal hernia repair techniques were used in 21.3% of the cases. The median follow-up time was 39.0 months (0-146, SD 35.3). The recurrence rates after the keyhole, Sugarbaker, sandwich, specific funnel-shaped mesh, and other techniques were 35.9%, 21.5%, 13.5%, 15%, and 35.3%, respectively. The overall re-operation rate was 20.4%, while complications occurred in 26.3% of patients. Conclusion The recurrence rate after parastomal hernia repair is unacceptable in this nationwide cohort study. As PSH repair volumes are low, further multinational, randomized controlled trials and hernia registry data are needed to improve the results.Peer reviewe

Methylation in Predicting Progression of Untreated High-grade Cervical Intraepithelial Neoplasia

BackgroundThere is no prognostic test to ascertain whether cervical intraepithelial neoplasias (CINs) regress or progress. The majority of CINs regress in young women, and treatments increase the risk of adverse pregnancy outcomes. We investigated the ability of a DNA methylation panel (the S5 classifier) to discriminate between outcomes among young women with untreated CIN grade 2 (CIN2).MethodsBaseline pyrosequencing methylation and human papillomavirus (HPV) genotyping assays were performed on cervical cells from 149 women with CIN2 in a 2-year cohort study of active surveillance.ResultsTwenty-five lesions progressed to CIN grade 3 or worse, 88 regressed to less than CIN grade 1, and 36 persisted as CIN1/2. When cytology, HPV16/18 and HPV16/18/31/33 genotyping, and the S5 classifier were compared to outcomes, the S5 classifier was the strongest biomarker associated with regression vs progression. The S5 classifier alone or in combination with HPV16/18/31/33 genotyping also showed significantly increased sensitivity vs cytology when comparing regression vs persistence/progression. With both the S5 classifier and cytology set at a specificity of 38.6% (95% confidence interval [CI], 28.4–49.6), the sensitivity of the S5 classifier was significantly higher (83.6%; 95% CI, 71.9–91.8) than of cytology (62.3%; 95% CI, 49.0–74.4; P = 0.005). The highest area under the curve was 0.735 (95% CI, 0.621–0.849) in comparing regression vs progression with a combination of the S5 classifier and cytology, whereas HPV genotyping did not provide additional information.ConclusionsThe S5 classifier shows high potential as a prognostic biomarker to identify progressive CIN2.</div

Parastomal Hernia: A Retrospective Nationwide Cohort Study Comparing Different Techniques with Long-Term Follow-Up

Background Parastomal hernia repair is a complex surgical procedure with high recurrence and complication rates. This retrospective nationwide cohort study presents the results of different parastomal hernia repair techniques in Finland. Methods All patients who underwent a primary end ostomy parastomal hernia repair in the nine participating hospitals during 2007-2017 were included in the study. The primary outcome measure was recurrence rate. Secondary outcomes were complications and re-operation rate. Results In total, 235 primary elective parastomal hernia repairs were performed in five university hospitals and four central hospitals in Finland during 2007-2017. The major techniques used were the Sugarbaker (38.8%), keyhole (16.3%), and sandwich techniques (15.4%). In addition, a specific intra-abdominal keyhole technique with a funnel-shaped mesh was utilized in 8.3% of the techniques; other parastomal hernia repair techniques were used in 21.3% of the cases. The median follow-up time was 39.0 months (0-146, SD 35.3). The recurrence rates after the keyhole, Sugarbaker, sandwich, specific funnel-shaped mesh, and other techniques were 35.9%, 21.5%, 13.5%, 15%, and 35.3%, respectively. The overall re-operation rate was 20.4%, while complications occurred in 26.3% of patients. Conclusion The recurrence rate after parastomal hernia repair is unacceptable in this nationwide cohort study. As PSH repair volumes are low, further multinational, randomized controlled trials and hernia registry data are needed to improve the results.</p