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Objective: Previous studies have shown associations between independent pre-conization variables (e.g. smoking, age, cytological grade, menopause) and positive or negative cone margins. However, it is not clear if these pre-surgical variables add predictive value to cone dimensions in the prediction of cone margin status. This study aimed to compare different models predicting positive ecto- or endocervical margins to assess whether pre-conization variables provide significant added value compared with cone dimensions alone., Study Design: One hundred and sixty-one consecutive women with high-grade cervical intra-epithelial neoplasia on cone specimens were analysed retrospectively. The sample was divided into women with positive ecto- or endocervical cone margins and women with negative ecto- or endocervical cone margins. Pre-conization clinical features, cone volume and cone length were included among the study variables. Multivariate stepwise regression analysis was used to create different models predicting incomplete cervical excision. The added value of pre-conization predictors was measured with receiver operating characteristic (ROC) curve comparisons., Results: Fifty-seven (35.4 %) women had incomplete cervical excision. Multivariate analysis showed that a positive ectocervical margin was significantly associated with low-grade cervical cytology [odds ratio (OR) = 0.25, 95 % confidence interval (CI) 0.09-0.70] and cone length (OR = 0.69, 95 % CI 0.58-0.82, criterion <9 mm). The area under the curve (AUC) of the combined model for prediction of a positive ectocervical margin was 0.78 (95 % CI 0.70-0.84, p < 0.001). A positive endocervical margin was associated with cone length (OR=0.78, 95 % CI 0.65-0.93, criterion <9 mm) and age (OR=1.07, 95 % CI 1.02-1.11, criterion ≥45 years). The AUC of the combined model for prediction of positive endocervical margin was 0.75 (95 % CI 0.66-0.82, p < 0.001). Comparison of ROC curves showed that the addition of pre-conization variables to cone length did not yield significant predictive results for either ecto- or endocervical cone margins (p = 0.228 and 0.349, respectively)., Conclusions: The addition of pre-conization clinical variables to cone dimensions did not improve the prediction of cone margin status significantly in the study cohort. Among cone dimensions, cone length was the best predictor of come margin status., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To assess the effect of age on pre- and post-conization HPV genotype distribution., Methods: The present retrospective observational study included consecutive women with high-grade cervical intraepithelial neoplasia who underwent conization at the Cervical Cancer Screening Centre of Reggio Emilia, Italy, and University Hospital of Modena, Italy, between February 1, 2012, and October 31, 2014. Pre-conization and 6-month post-conization HPV genotyping results were compared between four age groups (<30, 30-39, 40-49, and ≥50 years) and age-related changes in the HPV genotypes present were evaluated., Results: There were 162 patients included. The lowest occurrence of pre-conization high-risk and probable high-risk HPV genotypes was observed among patients aged at least 50 years when compared with younger patients (P=0.017). Conversely, women aged at least 50 years exhibited the highest level of post-conization high-risk and probable high-risk HPV genotypes (P=0.043). Additionally, an increasing incidence of recording identical pre- and post-conization HPV genotypes was associated with increasing age (P=0.024), as was increasing post-treatment recurrence of cervical intraepithelial neoplasia grade 2+ (P=0.030)., Conclusion: The presence of high-risk and probable high-risk HPV genotypes was lowest among older patients before conization and was highest among these patients post-conization; post-treatment HPV clearance decreased with age and increasing age could be a risk factor for post-conization recurrence., (© 2017 International Federation of Gynecology and Obstetrics.)

Background: The accumulation of cyclin-dependent kinase inhibitor 2A (p16 ink4a ) protein in a cell is associated with neoplastic progression in precancerous cervical lesions. Dual staining for p16 ink4a and Ki-67 has been proposed as a triage test in cervical cancer screening for women who test positive for human papillomavirus DNA. In this study, interobserver reproducibility of the interpretation of this test was assessed., Methods: Forty-two immunostained, liquid-based cytology slides were divided into 2 sets and were interpreted by 17 to 21 readers from 9 different laboratories, yielding a total of 816 reports. Immunostaining results were classified as positive, negative, inconclusive, or inadequate. After evaluation of the first set of slides and before circulation of the second set, the results were discussed in a plenary meeting. The 10 slides with the most discordant results were evaluated again by selected expert cytopathologists., Results: The overall κ value was 0.612 (95% confidence interval [CI], 0.523-0.701), it was higher for the positive and negative categories (κ = 0.692 and κ = 0.641, respectively), and it was almost null for the inconclusive category (κ = 0.058). Considering only readers from laboratories with documented experience, the κ value was higher (κ = 0.747; 95% CI, 0.643-0.839) compared with nonexperienced centers (κ = 0.498; 95% CI, 0.388-0.616). The results were similar in both sets of slides (κ = 0.505 [95% CI, 0.358-0.642] and κ = 0.521 [95% CI, 0.240-0.698] for the first and second sets, respectively). Reinterpretation of the slides with the most discordant results did not provide any improvement (first evaluation, κ = 0.616 [95% CI, 0.384-0.866]; second evaluation, κ = 0.403 [95% CI, 0.182-0.643])., Conclusions: Dual staining for p16 ink4a and Ki-67 demonstrated good reproducibility, confirming its robustness, which is a necessary prerequisite for its adoption as a triage test in cervical cancer screening programs that use human papillomavirus DNA as a primary test. Cancer Cytopathol 2017;125:212-220. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Background: The human papillomavirus (HPV) vaccine was conceived to prevent new HPV infections among uninfected young women. From the initial intentions, its use has been extended to older women and also tested as a therapeutic tool. We report two HPV vaccination outcomes during postconization follow-up., Cases: Two young women, with different clinical histories, were subjected to HPV vaccine after a loop electrosurgical excision procedure for high-grade cervical intraepithelial neoplasia (CIN) and persisting low-grade CIN. During follow-up both women experienced a worsening of cervical lesions, which resulted in invasive cervical cancer and severe dysplasia, respectively., Conclusion: Limited to our experience, a nonpersonalized HPV vaccine administration during postconization follow-up was expensive and unnecessary.

This study compares the incidence and treatments of cervical neoplasia in foreigners from high migration countries and Italians in the Reggio Emilia province (Northern Italy) in 2002-2009. Standardized incidence ratios (SIRs) and 95% confidence intervals (95% CI) for cervical intraepithelial neoplasia grade 3 (CIN3) and cancer were calculated for foreigners versus Italian women; foreigners were also classified according to the prevalence of human papillomavirus (HPV) in their country of origin. The proportion of hysterectomies is presented as an indicator of inappropriate surgery in CIN3 and microinvasive cancers. A higher risk was observed in women from high human papillomavirus prevalence countries (HHPVC) both for cancer and for CIN3 (SIR=4.1, 95% CI=2.2-6.9; SIR=2.0, 95% CI 1.7-2.5, respectively), whereas in those from low human papillomavirus prevalence countries (LHPVC), no difference for cancer and a lower risk for CIN3 were observed (SIR=1.0, 95% CI 0.2-2.2; SIR=0.6, 95% CI 0.4-0.8, respectively). A lower CIN3/cancer ratio was found in women from HHPVC (2.6) and in women from LHPVC (3.6) than in Italians (7.4). The percentage of hysterectomies for CIN3 or microinvasive cancers was 3.4 in foreigners and 4.7 in Italians. A higher risk of cervical cancer was found in women from HHPVC compared with Italians and women from LHPVC, suggesting a role of HPV prevalence in the country of origin in the excess risk. The CIN3/cancer ratio was lower for both women from HHPVC and women from LHPVC, also suggesting a role of low screening uptake for cervical cancer incidence in immigrants.

Objective: To identify the clinical/colposcopic variables that associate with low-grade/negative cone histology in screening-age women undergoing conization for high-grade cervical intraepithelial neoplasia (CIN). The follow-up outcomes of study participants were also compared., Study Design: In this retrospective cohort study, 585 consecutive screening-age women who underwent immediate conization for CIN2-3 were divided according to cone histology (CIN2+ versus ≤CIN1) and assessed in relation to clinical/colposcopic variables by univariate and multivariate analyses., Results: Low-grade [adjusted odds ratio (AOR)=52.67, 95% confidence interval (CI) 22.49-123.34] or normal (AOR=9.81, 95% CI 2.38-40.44) colposcopic impression and CIN2 on cervical biopsy (AOR=19.59, 95% CI 6.62-57.92) associated with CIN1/negative cone histology. Multivariate analysis also showed that Eastern European ethnicity (AOR=0.13, 95% CI 0.03-0.52) and high-risk-Human Papillomavirus (hr-HPV)-positivity (AOR=0.38, 95% CI 0.17-0.87), associated with CIN2+ cone histology. Overall, there were no significant differences between the two groups in terms of high-grade recurrence during the 2-year follow-up. Conversely, a higher rate of high-grade recurrence was present in CIN2-3 (positive cone margins) than in CIN1/negative cone histology (21.9% versus 7.4%, P=0.008, respectively)., Conclusion: The presence of CIN2 on cervical biopsy and a low-grade colposcopic impression were predictive of a minor cone histology, unless the subject was of East European ethnicity or was positive for hr-HPV test. Given the follow-up outcomes, the same women need to perform a close monitoring. However, positive cone margins in women with CIN2-3 cone histology seem to define a population at greater risk of high-grade recurrence., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To evaluate the effect of age on the diagnostic assessment of women with severe cervical intraepithelial neoplasia (CIN)., Methods: This retrospective observational study included 338 consecutive women with a diagnosis of CIN3 on cone specimen. Patients were divided into three groups according to age: < 35 years (Group A), 35-49 years (Group B), and ≥ 50 years (Group C). Clinical and colposcopic variables were compared, and human papillomavirus (HPV) genotype distribution was measured., Results: The most common HPV genotype was HPV-16 (63.65%), followed by HPV-33 (7%), HPV-18 (6.2%), and HPV-31 (5.4%). The rate of the following high-grade lesion predictors was lower in Group C than in Groups A and B: HPV-16 infections (55.9% vs. 75% vs. 70.9%, respectively, p = 0.022); high-grade colposcopic impression (29.4% vs. 51.8% vs. 51.7%, respectively, p < 0.0001); and high-grade cytological changes (30.9% vs. 56.2% vs. 45.4%, respectively, p = 0.025). An endocervical lesion location was more frequent in Group C than in Groups A and B (55.6% vs. 6.8% vs. 11.8%, respectively, p < 0.0001)., Conclusion: Women aged 50 years and older with CIN3 showed a significant reduction of high-grade lesion predictors along with physiological confounding cervical changes (transformation zone type 3 and endocervical lesion location). The diagnostic work-up of cervical lesions in older women should provide their potential consideration as a special population.

Purpose: To create a prediction model of high-grade cervical intraepithelial neoplasia (CIN) based on clinical variables and the cervical nitric oxide metabolite (NOx) levels of study participants., Methods: This comparative study included 694 women undergoing colposcopy due to abnormal pap smear results. On the basis of the cervical biopsy results, the women were divided into the ≤ CIN 1 or CIN 2-3 group. The two groups were compared in terms of cervical NOx levels and clinical variables. Univariate, multivariate, and receiver-operating characteristic curve analysis were performed., Results: Multivariate analysis showed that CIN 2-3 associated with more than two cervical biopsies [odds ratio (OR) = 5.16], high-grade squamous intraepithelial lesion cytology (OR = 16.19), condom non-use (OR = 4.28), cervical NOx levels ≤ 99.9 μmol/L (OR = 16.62), more than four lifetime male sexual partners (OR = 10.56), and age at first coitus of ≤ 15 years old (OR = 3.54). This combined model had a sensitivity of 86.49 %, a specificity of 90.74 %, a positive predictive value of 64.0 %, and a negative predictive value of 97.2 %., Conclusions: In the present sample, high-grade CIN associated with decreased cervical NOx levels. Thus, along with some clinical variables, cervical NOx levels may be an additional marker of cervical dysplasia.

Aim: The aim of this study was to compare the psychological impact of loop electrosurgical excision procedure (LEEP) in pre- and postmenopausal women., Material and Methods: This was an observational comparative study including 231 pre- and 108 post-menopausal women undergoing LEEP who were subjected to an interview inquiring specific psychological domains concerning the impact of this surgical procedure. The associations between women's answers and their hormonal status were tested by logistic regression analysis., Results: Multivariate analysis showed that after LEEP, postmenopausal women were associated with answers that indicated significant psychological changes concerning the impact of cervix disease (Odds Ratio [OR] = 2.38, 95% Confidence Interval [CI] 1.22-4.66), their body image (OR = 6.80, 95% CI 2.30-20.08), interpersonal relationship with their partner (OR = 8.32, 95% CI 1.77-38.99) and sexual health quality (OR = 2.25, 95% CI 1.15-4.39)., Conclusion: Limited to our sample, the psychological impact of LEEP seems to be greater in postmenopausal than in premenopausal women. We speculate that LEEP could cause failure of psychological domains already weakened by menopause., (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)

High-risk human papillomaviruses (HPV) are largely implicated in the carcinogenesis of cervical carcinomas. Their role in lung carcinomas, however, is still unclear. We describe the case of 44-year-old female chain-smoker with previous HPV-related cervical cancer and a new distant tumour in the lung after many years. The histologic distinction between metastatic squamous cell carcinoma of the cervix and another primary squamous cell tumour of the lung can be difficult and has important clinical implications. The aim of our study was to investigate whether HPV was present in both the patient's cervical cancer and her subsequent primary lung cancer in order to appropriately plan therapy. We tested both the paraffin-embedded tissue of the cervical cancer and the lung cancer for HPV DNA using the Qiagen HPV Sign Genotyping Test, which detected HPV16-DNA in both tumours. The Qiagen HPV Sign Genotyping Test is a reliable method to detect HPV-DNA in tissue and cytological materials, thus making it possible to distinguish metastatic cervical carcinoma from a new primary tumour in different sites.

Within a multicentre controlled trial framework, an external quality control (EQC) was scheduled to evaluate the interlaboratory reproducibility of liquid-based cytology. In particular, this EQC intended to evaluate the reproducibility of the ASCUS diagnosis.A selected set of 30 slides (4 within normal limit cases, 16 atypical squamous cells of undetermined significance; 4 low-grade squamous intraepithelial lesions and 6 high-grade squamous intraepithelial lesions) circulated among the 13 laboratories involved in the trial.Kappa values were obtained from the comparison between individual laboratory diagnoses and majority diagnoses with target diagnoses. Specific kappa values resulted moderate to high for HSIL and low to moderate for LSIL and WNL. Meanwhile, the specific kappa for ASCUS was below 0.4 in 12 of 13 participating laboratories. The lack of reproducibility for ASCUS was not a result of the introduction of this new technology but rather to the low reproducibility of the ASCUS category itself stemming from intrinsic uncertainties in the reporting criteria., ((c) 2007 Wiley-Liss, Inc.)

Objectives: To evaluate the frequency and correlates of non-adherence to follow-up among patients conservatively treated for CIN2-3., Study Design: Study population comprised 1560 patients aged 25-64 years from a screening programme in northern Italy. The regional standard protocol was used as a reference. Multinomial logistic regression analysis was used to estimate the odds ratio probability of a patient being lost to follow-up (no check-ups within 27 months of treatment) or incompletely followed-up (1-3 negative check-ups) versus having 4 negative check-ups., Results: Three hundred twenty-six patients (21%) were lost to follow-up, 678 (43%) were incompletely followed-up, 352 (23%) presented for 4 negative check-ups and 204 (13%) were diagnosed with persistent disease. The probability of no or incomplete follow-up was greater for patients who lived in the urban district, who were treated in private settings (versus screening centres), who exhibited a visibile squamocolumnar junction on pre-treatment colposcopy, who were treated with cold knife excision and local destructive therapy (versus loop diathermy excision), and whose surgical specimens had positive excision margins., Conclusions: Adherence to the reference protocol was poor. Factors involved in follow-up failures require greater clinical attention.

Background: The degree of applicability of the Bethesda System 2001 (TBS 2001) for cervicovaginal cytology to a public health setting is unknown, and extrapolations from available data are unwarranted., Methods: A "before/after" study design was used to evaluate the impact of TBS 2001 on an organized, population-based screening program in northern Italy. Between 2003-2004, 6 cytology laboratories converted from TBS 1991 to TBS 2001. A set of screening indicators based on TBS 2001 (85,012 patients) were compared with those based on TBS 1991 (199,833 patients) by means of their laboratory- and patient age-standardized ratio with a 95% confidence interval (CI)., Results: The prevalence of cervical intraepithelial neoplasm (CIN)2-3/carcinoma was stable between the 2 populations. TBS 2001 had no effect on the unsatisfactory rate (1.99% vs. 2.03% for TBS 1991) nor on follow-up compliance rate (93.2% vs. 92.3%). The reporting rate of atypical squamous cells (ASC) decreased from 17.1 to 14.7 per 1000 (ratio, 0.86; 95% CI, 0.81-0.91), the total positivity rate from 31.1 to 29.0 per 1000 (ratio, 0.93; 95% CI, 0.90-0.97), and the ASC:SIL (squamous intraepithelial lesion) ratio from 1.38 to 1.16. Compared with the ASCUS (ASC of undetermined significance) reports of TBS 1991, the predictive value for CIN2-3/carcinoma decreased from 5.2 to 3.5% (ratio, 0.68; 95% CI, 0.48-0.93) among ASCUS reports, but increased from 5.1 to 17.2% (ratio, 3.41; 95% CI, 1.64-6.28) among ASC-cannot exclude high grade lesion (ASC-H) reports. ASC-H had a 5.01-fold (95% CI, 2.23-10.2) greater predictive value than ASCUS., Conclusions: TBS 2001 is applicable to cervical screening in a public health setting., ((c) 2006 American Cancer Society.)

The study was aimed at assessing interlaboratory reproducibility in the reporting of cervical smears in the atypical squamous cells of undetermined significance (ASCUS) category. A set of 50 selected slides circulated among 89 laboratories, currently involved in population-based screening programmes for cervical cancer, which provided a diagnostic report according to four main reporting categories based on the 1991 Bethesda system. Interlaboratory agreement was determined according to kappa (K) statistics: overall and weighted K values were determined for each laboratory and for single reporting categories. The results showed a very low reproducibility for the ASCUS category. This finding supports the Bethesda system 1991 recommendation to limit the use of this reporting category and suggests that the clinical response to ASCUS reports should be decided locally, based on the observed positive predictive value for cervical intraepithelial neoplasia 2 or more severe lesions.