Assisted Diagnosis of Cervical Intraepithelial Neoplasia (CIN)

This paper introduces an automated computer- assisted system for the diagnosis of cervical intraepithelial neoplasia (CIN) using ultra-large cervical histological digital slides. The system contains two parts: the segmentation of squamous epithelium and the diagnosis of CIN. For the segmentation, to reduce processing time, a multiresolution method is developed. The squamous epithelium layer is first segmented at a low (2X) resolution. The boundaries are further fine tuned at a higher (20X) resolution. The block-based segmentation method uses robust texture feature vectors in combination with support vector machines (SVMs) to perform classification. Medical rules are finally applied. In testing, segmentation using 31 digital slides achieves 94.25% accuracy. For the diagnosis of CIN, changes in nuclei structure and morphology along lines perpendicular to the main axis of the squamous epithelium are quantified and classified. Using multi-category SVM, perpendicular lines are classified into Normal, CIN I, CIN II, and CIN III. The robustness of the system in term of regional diagnosis is measured against pathologists' diagnoses and inter-observer variability between two pathologists is considered. Initial results suggest that the system has potential as a tool both to assist in pathologists' diagnoses, and in training

Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy : multicentre randomised controlled trial

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Prevalence of cervical disease at age 20 after immunisation with bivalent HPV vaccine at age 12-13 in Scotland: retrospective population study

The manuscript was reviewed by Jo’s Trust, which supports the conclusions. It made the following statement: We think (it has) massive implications for the screening programme, vaccine and also impact on diagnoses in the future. It gives weight for activity to increase vaccine uptake, has implications on screening intervals. The clinically relevant herd protection is very interesting too. It also feeds into our policy calls for a new IT infrastructure (for the screening programme in England) to record and enable invitations based on whether someone has at the vaccine if intervals can be extended. Funding: This study has been undertaken as part of the programme of surveillance of immunisation against human papillomavirus in Scotland, included within the routine work of Health Protection Scotland, a part of the Scottish National Health Service. No funding has been received from industry.Peer reviewedPublisher PD

Recurrence of cervical intraepithelial lesions after thermo-coagulation in HIV-positive and HIV-negative Nigerian women

Background: The burden of cervical cancer remains huge globally, more so in sub-Saharan Africa. Effectiveness of screening, rates of recurrence following treatment and factors driving these in Africans have not been sufficiently studied. The purpose of this study therefore was to investigate factors associated with recurrence of cervical intraepithelial lesions following thermo-coagulation in HIV-positive and HIV-negative Nigerian women using Visual Inspection with Acetic Acid (VIA) or Lugol’s Iodine (VILI) for diagnosis. Methods: A retrospective cohort study was conducted, recruiting participants from the cervical cancer “see and treat” program of IHVN. Data from 6 sites collected over a 4-year period was used. Inclusion criteria were: age ≥18 years, baseline HIV status known, VIA or VILI positive and thermo-coagulation done. Logistic regression was performed to examine the proportion of women with recurrence and to examine factors associated with recurrence. Results: Out of 177 women included in study, 67.8 % (120/177) were HIV-positive and 32.2 % (57/177) were HIV-negative. Recurrence occurred in 16.4 % (29/177) of participants; this was 18.3 % (22/120) in HIV-positive women compared to 12.3 % (7/57) in HIV-negative women but this difference was not statistically significant (p-value 0.31). Women aged ≥30 years were much less likely to develop recurrence, adjusted OR = 0.34 (95 % CI = 0.13, 0.92). Among HIV-positive women, CD4 count <200cells/mm3 was associated with recurrence, adjusted OR = 5.47 (95 % CI = 1.24, 24.18). Conclusion: Recurrence of VIA or VILI positive lesions after thermo-coagulation occurs in a significant proportion of women. HIV-positive women with low CD4 counts are at increased risk of recurrent lesions and may be related to immunosuppression

Preterm birth after loop electrosurgical excision procedure (LEEP). how cone features and microbiota could influence the pregnancy outcome

OBJECTIVE: In the last years, the mean age of women who underwent cervical treatment for high-grade cervical intraepithelial neoplasia (CIN 2-3) is similar to the age of women having their first pregnancy. The aim of this study was to evaluate the risk of preterm birth in subsequent pregnancies after loop electrosurgical excision procedure (LEEP). PATIENTS AND METHODS: From January 2013 to January 2016 the study identified a total of 1435 women, nulliparous, who underwent LEEP for CIN 2-3, and who wished to have their first pregnancy. Before surgery, the lengths of the cervix were calculated by transvaginal sonography. After the treatment, the dimension of the removed tissue was evaluated. During the pregnancy, all women carried out periodic transvaginal sonography and vaginal-cervical swabs. RESULTS: The average age of patients was 31.96±5.24 years; the interval between the surgical procedure and pregnancy was 12.04±4.67 months; the gestational age at births was 37.53±2.91 weeks. The first vaginal and cervical swab performed during pregnancy was negative in 81.8% of patients. The most prevalent infections were related to C. Albicans, G. Vaginalis, and Group B Streptococcus (GBS). The rate of preterm delivery was significantly higher in women with a minor cervical length. CONCLUSIONS: The length and the volume of cervical tissue excised have been shown to be directly related to the risk for preterm birth. Furthermore, vaginal infections and their persistence during pregnancy in women with a history of LEEP may be associated with an increased risk for preterm birth, compared with women with no history of LEEP

The effect of cervical intraepithelial neoplasia and treatment surgeries on fecundability

INTRODUCTION: Approximately 6 million couples in the United States experience infertility. Because few risk factors for infertility are known, identification of modifiable determinants is an important public health goal. Cervical intraepithelial neoplasia, CIN, occurs when the surface cells of the cervical tissue begin to change, and is caused by infection with a high-risk type of human Papillomavirus (HPV). CIN may affect the cervix’s immunological function, resulting in changes in mucus production, reduced protection against infections, and alterations in sperm transport through the cervical canal. CIN can also progress to invasive cervical cancer. There are four main CIN treatment procedures that aim to remove pre-cancerous cells from the cervix; loop excisions, commonly known as electrosurgical excision procedure (LEEP) or large loop excision of the transformative zone (LLETZ); cryosurgery; conization; and laser ablation. Because the goal of these procedures is to remove abnormal cells, healthy cervical cells may inadvertently be removed as well, leading to further changes in cervical mucus production, sperm motility, and reduced protection against infection. Because of the changes to the cervical tissue and its function, CIN and its surgical treatments may affect fecundability. METHODS: We analyzed data from Pregnancy Study Online (PRESTO), a preconception cohort of 5,594 North American pregnancy planners enrolled and followed between 2013 and 2018. At baseline, participants reported whether they had abnormal Pap tests and their age at their first abnormal Pap test, as well as cervical procedures and their age at the procedure. We estimated fecundability ratios (FR) and 95% confidence intervals (CI) using proportional probabilities models adjusted for sociodemographics, smoking, number of sexual partners, history of sexually transmitted infections/ pelvic inflammatory disease, and HPV vaccination. RESULTS: A history of abnormal Pap test, which we used as a proxy for cervical dysplasia, was positively associated with current and past smoking, gravidity, parity, irregular menses, number of sexual partners, history of chlamydia, genital warts and herpes, as well as a history of pelvic inflammatory disease. Of the women with an abnormal Pap test, the average age at first abnormal Pap test was 23.0 (std=4.5) years and the average number of abnormal Pap tests was 2.1 (std=1.7). We found little association overall between a history of abnormal Pap test and fecundability (FR=1.03, 95% CI: 0.96, 1.11). The results did not differ when the data were examined by number of abnormal Pap tests, or type of procedure. There was also little association between time since the diagnosis or procedure and pregnancy attempt and fecundability. There was however a slight decrease in fecundability within the first 2 years of diagnosis/ procedure, with FRs that tended to increase with increasing time since diagnosis/procedure. DISCUSSION: We found little association overall between a history of abnormal Pap test or cervical dysplasia, including excisional surgeries, and fecundability. These results are consistent with most other studies demonstrating no clear adverse effects of CIN and treatments. Recency of diagnosis or procedure did not appreciably affect these findings. Although we found a very slight decrease in fecundability within the first two years since diagnosis or procedure, fecundability became similar to that of undiagnosed/untreated women after 2 years, and then increased slightly. CONCLUSION: We found little association between a history of abnormal Pap and CIN treatments and fecundability. A major limitation of our study is that the data were self-reported, which may have resulted in non-differential exposure misclassification

Early discharge of low-risk women from cervical screening

Background: The Scottish Cervical Screening Programme currently offers three-yearly screening to all women between the ages of 20 and 60. However, previous studies have indicated that well-screened women over the age of 50 are likely to be at low risk of cervical neoplasia. This study aimed to explore the implications of discharging these women from screening in a typical area of Scotland. Methods: A case–control study of the screening histories of women with and without screen-detected cervical neoplasia between ages 50 and 59 in Lanarkshire was carried out, as well as a cross-sectional study of the prevalence of adequate screening histories among women currently aged 50 in Lanarkshire. Routine screening programme statistics were used to estimate the effects of introducing an early discharge policy. Results: Women reaching the age of 50 with two recent, consecutive, negative smears had reduced odds of screen-detected neoplasia in the subsequent decade. The estimated odds ratio for all screen-detected neoplasia (CIN 1–3, adenocarcinoma in situ and invasive carcinoma) was 4.4 [95 per cent confidence interval (CI) 1.6–13.2, p = 0.002]. The estimated odds ratio for screen-detected high-grade CIN and invasive squamous carcinoma was 17.0 (95 per cent CI 2.4–243.0, &#254; = 0.0004). A total of 54.0 per cent (95 per cent CI 47.9–59.9 per cent) of screening participants currently aged 50 fulfilled the definition of adequate screening. Discharging these women might be expected to reduce screening workload by approximately 10 per cent, but those discharged would be at increased risk of neoplasia. Conclusion: Now that full screening histories are available in all health board areas since 1990, the identification of a low-risk group within the screened population could be the first step towards a screening programme targeted more closely on those with the greatest capacity to benefit

Diagnosis of Cervical Cancer and Pre-Cancerous Lesions by Artificial Intelligence: A Systematic Review

The likelihood of timely treatment for cervical cancer increases with timely detection of abnormal cervical cells. Automated methods of detecting abnormal cervical cells were established because manual identification requires skilled pathologists and is time consuming and prone to error. The purpose of this systematic review is to evaluate the diagnostic performance of artificial intelligence (AI) technologies for the prediction, screening, and diagnosis of cervical cancer and pre-cancerous lesions

Conização, exame de congelação e histerectomia planejada no tratamento de neoplasia intra-epitelial de alto grau

PURPOSE: We tested the role of frozen section examination of the cone specimen in the evaluation of the resection margin status and to rule out invasion in patients with high-grade cervical intraepithelial neoplasia. METHODS: Twenty-five patients with cervical intraepithelial neoplasia underwent conization followed by frozen section examination and planned hysterectomy. The results of the definitive paraffin exam were compared with frozen section examination. RESULTS: In the evaluation of the margins by frozen section examination, 16 patients (64%) had positive cone margins and 9 (36%) had negative margins. The definitive paraffin examination of margin status was concordant in all the cases. Intraoperative diagnosis of invasion was made in 5 cases, and 1 of these was microinvasive. Among the remaining 20 cases, we detected 2 additional microinvasive carcinomas after paraffin study, so the diagnosis of the frozen section examination was concordant with the paraffin sections in 23/25 cases (92%). Two cases of microinvasive carcinoma were diagnosed as cervical intraepithelial neoplasia by frozen section examination and had less than 2 mm stromal invasion. CONCLUSIONS: In high-grade cervical intraepithelial neoplasia, frozen section examination can provide immediate and precise evaluation of the cone margin status in high-grade cervical intraepithelial neoplasia. It can identify frank invasion and permit adequate treatment in a one-stage procedure. In early microinvasive disease, frozen section examination fails to detect the area of invasion but reliably detects clear resection margins.OBJETIVOS: Foi avaliado o papel do exame intra-operatório de congelação no diagnóstico de invasão e no estado das margens cirúrgicas em pacientes com neoplasia intra-epitelial de alto grau. CASUÍSTICA E MÉTODO: Vinte e cinco pacientes com neoplasia intra-epitelial de alto grau foram submetidas a conização cervical seguida de histerectomia. O resultado do exame definitivo em parafina foi comparado com o exame de congelação. RESULTADOS: Dezesseis pacientes (64 %) tiveram margens comprometidas e 9 (36 %) livres. O diagnóstico definitivo na parafina foi concordante em todos os casos no diagnóstico do estado das margens. Em cinco casos foi diagnosticada invasão, sendo 1 caso de carcinoma microinvasivo. Entre os 20 casos restantes foram detectados 2 carcinomas microinvasivos adicionais após o exame em parafina. Desta forma o exame intra-operatório de congelação foi concordante com o exame definitivo em 23/25 casos (92 %). Dois casos de carcinoma microinvasivo foram diagnosticados como neoplasia intra-epitelial de alto grau no exame de congelação e apresentavam invasão estromal menor que 2 cm. CONCLUSÕES: O exame intra-operatório de congelação é capaz de predizer o estado das margens cirúrgicas em todos os casos de neoplasia intra-epitelial de alto grau assim como o diagnóstico de invasão franca. Nos casos de carcinoma microinvasivo este exame falha na detecção de invasão, entretanto é capaz de garantir margens livres de ressecção

Expenditure and resource utilisation for cervical screening in Australia

BACKGROUND The National Cervical Screening Program in Australia currently recommends that women aged 18-69 years are screened with conventional cytology every 2 years. Publicly funded HPV vaccination was introduced in 2007, and partly as a consequence, a renewal of the screening program that includes a review of screening recommendations has recently been announced. This study aimed to provide a baseline for such a review by quantifying screening program resource utilisation and costs in 2010. METHODS A detailed model of current cervical screening practice in Australia was constructed and we used data from the Victorian Cervical Cytology Registry to model age-specific compliance with screening and follow-up. We applied model-derived rate estimates to the 2010 Australian female population to calculate costs and numbers of colposcopies, biopsies, treatments for precancer and cervical cancers in that year, assuming that the numbers of these procedures were not yet substantially impacted by vaccination. RESULTS The total cost of the screening program in 2010 (excluding administrative program overheads) was estimated to be A$194.8M. We estimated that a total of 1.7 million primary screening smears costing$96.7M were conducted, a further 188,900 smears costing $10.9M were conducted to follow-up low grade abnormalities, 70,900 colposcopy and 34,100 histological evaluations together costing$21.2M were conducted, and about 18,900 treatments for precancerous lesions were performed (including retreatments), associated with a cost of $45.5M for treatment and post-treatment follow-up. We also estimated that$20.5M was spent on work-up and treatment for approximately 761 women diagnosed with invasive cervical cancer. Overall, an estimated $23 was spent in 2010 for each adult woman in Australia on cervical screening program-related activities. CONCLUSIONS Approximately half of the total cost of the screening program is spent on delivery of primary screening tests; but the introduction of HPV vaccination, new technologies, increasing the interval and changing the age range of screening is expected to have a substantial impact on this expenditure, as well as having some impact on follow-up and management costs. These estimates provide a benchmark for future assessment of the impact of changes to screening program recommendations to the costs of cervical screening in Australia