High-grade Cervical Intraepithelial Neoplasia Research Articles

Cervical intraepithelial neoplasia in non-16/18 high-risk human papilloma virus positive/cytology negative women: An alternative approach in poor resource areas.

Because the specific prevalence and carcinogenesis of non-16/18 high-risk (hr) Human Papillomavirus (HPV) is not fully understood, we designed a study with aim of evaluating the risk of high-grade cervical intraepithelial neoplasia (CIN) in non-16/18 hr-HPV positive/cytology negative cases and assessing the distribution of non-16/18 hr-HPV subtypes. This cross-sectional study was conducted on 138 non-16/18 hr-HPV positive/cytology negative women, who were referred to the gynecologic oncology clinic of Yas hospital, affiliated with Tehran University of Medical Sciences, January 2021 to 2022. Among the detected types, HPV 31 was the most frequent type. 63 cases underwent biopsy as indicated based on colposcopic examination with acetic acid 3% application among which 34 had normal results. In the remaining 29 cases, 25 had insignificant findings. CIN2 was reported in 2 cases, one with HPV 31, 45, 58, and the other with HPV 58. CIN3 was also detected in 2 cases, one with HPV 31 and the other with HPV 35, 45. The overall incidence of high-grade CIN was 2.8%. A statistically significant (P-value=0.046) difference was detected between patients with high-grade CIN compared with the others regarding the Hookah usage. The risk of CIN among non-16/18 hr-HPV positive/cytology negative cases is noticeably low. Based on ASCCP guidelines return testing at 1 year without immediate colposcopy seems sufficient; however, because of many reasons doing immediate colposcopy rather than 1-year follow-up may be a more accessible approach in resource poor, low-income countries such as ours.

Prediction of cervical cancer precursor lesions by quantitative methylation specific PCR: A retrospective study.

This study was undertaken to evaluate the performance of FAM19A4 and hsa-mir-124-2 hypermethylation as a triage tool for women who are at risk of developing cervical cancer or high-grade cervical cancer precursor lesions by taking into consideration the cytology report, histology diagnosis, and human papillomavirus (HPV) status. A total of 330 cervical ThinPrep samples were retrospectively collected and used for DNA isolation. HPV DNA was detected by real-time polymerase chain reaction (PCR), and HPV genotypes were identified by Sanger-based sequencing. DNA extracts were bisulphite-treated, and hypermethylation of FAM19A4 and hsa-mir-124-2 genes was detected by a quantitative methylation-specific PCR (qMSP) test using the QIAsure Methylation assay. Hypermethylated genes were detected in 27 (9.6%) cervical samples, mostly found in women diagnosed with high-grade squamous intraepithelial legions (77.8%) or cervical intraepithelial neoplasia grade 3 (CIN3) (72.7%). The sensitivity and the specificity of the qMSP test for predicting CIN3 lesions among women with high-risk HPV was 75% and 91%, respectively. There was a significant correlation between high-grade cervical cancer precursor lesions and detection of hypermethylated genes in samples positive for high-risk HPV. Our results suggest that the QIAsure Methylation test can be used as a triage tool to identify women at risk for cervical cancer progression.

Complications of Loop Electrosurgical Excision Procedure Following Treatment of Cervical Intra-Epithelial Neoplasia 2 & 3

Background: The loop electrosurgical excision procedure (LEEP) is currently one of the most commonly used approaches to treat high grade cervical squamus intraepithelial lesion confirmed on colposcopic guided biopsy examination. Complications of electrosurgical excision procedure (LEEP) are rare. But in Bangladesh, we have very limited research-based information regarding this issue. Aim of the Study: The aim of the study was to assess the complications of loop electrosurgical excision procedure following treatment of cervical intra-epithelial neoplasia (CIN) 2 and 3. Methods: This descriptive cross-sectional study was conducted in OPD, Gynaecology and Obstetrics Department, Rangpur Medical College Hospital, Rangpur, Bangladesh during the period of July 2011 to June 2012. In total, 75 patients with CIN 2 and/or 3 were enrolled in this study as study subjects. The study was approved by the ethical committee of the mentioned hospital. Proper informed written consents were taken from all the participants before data collection. The criteria for inclusion were colposcopic guided biopsy revealing CIN 2 or 3 whose lesion remains confined to ectocervix. The least amount of power that will effectively perform the electrosurgery should be used, so as to minimize the risk to the patient’s normal tissues and ensure that the excised specimen is inacceptable condition for pathological assessment. Data analysis was done by using statistical package for social science (SPSS) 16 versions. Results: In analyzing the post procedure complications of the participants, we observed that, 64% participants were from vaginal discharge. Besides this 21%, 9%, 4% and 1% cases were found with pain, bleeding, fever and cervical stenosis consequently. Distributing persistence of vaginal discharge, 44% participants taken 5-10 days which was noticeable. Only 5.33% participants had vaginal discharge in between 21-25 days. In distributing persistence of pain, we observed that, 8% participants had taken 30 days to be cured which was the highest number of patients. Within one week, all the patients become free from fever. Cervical Stenosis occurred as a delayed complication during follow up at 9-12 months after LEEP in only 1(1.3%) case and occurred at 270th day. Conclusion: As per the findings of this study we can mention vaginal discharge as the most common complication for the cervical intra-epithelial neoplasia patients by treating loop electrosurgical excision procedure. Besides these, physicians should be aware about the sufferings of patients from pain and bleeding. Finally, we can conclude that, LEEP as an easy safe and acceptable treatment for high grade CIN with high cure rate.

Practical application of modified ASCCP 2019 algorithms in the diagnosis and early detection of cervical pathology.

We assessed the risk for the high-grade precancerous CIN 2 (+) in women with HSIL and ASC-H depending on HPV status. A retrospective analysis of results of cervical cancer screening following the current ASCCP recommendations by co-testing (LBC and molecular HPV DNA HR) performed between 2018 and 2022 in the Laboratory of Cervical Pathology, Obstetrics and Gynecology Hospital of Poznan University of Medical Sciences. Patient ages ranged from 22 to 72 years. The analysis of abnormal results of liquid-based cytology revealed the following: 1 suspicion of cervical carcinoma, 49 HSIL, 97 ASC-H, 95 LSIL, 92 ASCUS, and 4 AGC cases. Histopathological verification of the biopsy samples revealed a total of 288 abnormal results. CIN 2 (+) lesions were found in 127 women. ASC-H was the most common abnormal cytologic finding. Of the 338 molecular test results for HPV DNA HR, 85% were confirmed positive. A positive molecular signal confirming the presence of human papillomavirus on PAP smear was not homonymous with simultaneous histopathological diagnosis of cervical pathology. There is a high risk for CIN 2 (+) in patients with HSIL and HPV 16 (+) and/or HPV DNA HR (+), as well as ASC-H and HPV 16 (+). HSIL is rarely observed in women with HPV 16 (-). The risk for CIN 2 (+) in women with ASC-H and HPV (-) is low.

Detection of high-grade cervical neoplasia using extended genotyping: Performance data from the longitudinal phase of the Onclarity trial

ObjectivesThe Onclarity cervical cancer screening trial was designed to establish the clinical validity of the Onclarity HPV assay for extended genotyping (xGT) during detection of high-grade cervical neoplasia grades 2 or 3 (≥CIN2 or ≥CIN3). Here, three-year follow up data is presented to evaluate the overall efficacy of these screening strategies, compared to the baseline data. MethodsAt baseline 29,513 women, ≥25 years, had evaluable cytology and valid high-risk HPV results. Women with atypical squamous cells-undetermined significance or worse cytology or a positive HPV test were referred for colposcopy/biopsy. Participants that did not reach the study end point (treatment for ≥CIN2) continued into the longitudinal phase that included the same protocol as baseline. ResultsThe three-year cumulative incident risk (CIR) for ≥CIN3 in HPV-negative women was 0.15% [95%CI: 0.06, 0.26] and for HPV- and cytology-negative women was 0.12% [95% CI: 0.03,0.23]. HPV16 carried the highest baseline and three-year ≥CIN3 CIR, followed by HPV31 and HPV18. At least one year of genotype-specific persistence increased ≥CIN3 risk for xGT results compared to genotype non-persistence, HPV clearance, or new infection over the same time period. Risk-based screening with immediate colposcopy for HPV16/18/31 and further xGT triage resulted in better ≥CIN3 sensitivity (79.2% versus 72.3%; relative difference of 6.9 [95%CI: 3.3, 10.4]) and a lower colposcopy/≥CIN3 ratio (9.2 versus 11.2; relative difference of −1.9 [95%CI: −2.6, −1.3]) when compared to primary HPV16/18-based screening. ConclusionsAn HPV-negative result offers the same assurance of no disease over three years of follow up as that offered by a negative co-testing result. xGT facilitates risk-based screening and persistence tracking and can help optimize disease detection during screening without excessive colposcopic procedures.

Comparison of HPV 16/18 Genotyping and p16/Ki67 Dual Staining for Detection of High-Grade Cervical Lesion in Patients with Low-Grade Cervical Smears.

To triage low-grade cervical smears (ASCUS/LSIL) by HPV 16/18 genotyping and dual staining with p16/Ki67 and to compare the sensitivity and specificity of these two triage methods for detection of high-grade cervical intraepithelial neoplasia (HGCIN). In this prospective cross-sectional study, we evaluated a total of 89 women with low-grade smears (54 ASCUS, 35 LSIL) recruited from a tertiary care hospital. All patients underwent colposcopy guided cervical biopsy. Histopathology was used as gold standard. All samples were subjected to HPV 16/18 genotyping (excluding 9) using DNA PCR and p16/Ki67 dual staining (excluding 4) using Roche® kit. We then compared the two triage methods to detect high-grade cervical lesions. Overall, in all low-grade smears sensitivity, specificity and accuracy of HPV 16/18 genotyping, was found to be 66.7%, 77.1% and 76.2% respectively (p = 0.03). In low-grade smears sensitivity, specificity and accuracy of dual staining, was found to be 66.7%, 84.8% and 83.5% respectively (p = 0.01). Overall, in all low-grade smears the sensitivity of the two tests was comparable. However, dual staining had a higher specificity and accuracy than HPV 16/18 genotyping. It was concluded that both are effective triage methods but dual staining had a better performance than HPV 16/18 genotyping.

Micronutrients and prevention of cervical pre-cancer in HPV vaccinated women: a cross-sectional study.

Prophylactic vaccines against high-risk human papillomaviruses (HR-HPVs) hold promise to prevent the development of higher grade cervical intraepithelial neoplasia (CIN 2+) and cervical cancer (CC) that develop due to HR-HPV genotypes that are included, in HPV vaccines, but women will continue to develop CIN 2+ and CC due to HR-HPV genotypes that are not included in the quadrivalent HPV vaccine (qHPV) and 9-valent HPV vaccine (9VHPV). Thus, the current vaccines are likely to decrease but not entirely prevent the development of CIN 2+ or CC. The purpose of the study was to determine the prevalence and determinants of CIN 2+ that develop due to HR-HPVs not included in vaccines. Study population consisted of 1476 women tested for 37 HPVs and known to be negative for qHPVs (6/11/16/18, group A, n = 811) or 9VHPVs (6/11/16/18/31/33/45/52/58, group B, n = 331), but positive for other HR-HPVs. Regression models were used to determine the association between plasma concentrations of micronutrients, socio-demographic, lifestyle factors and risk of CIN 2+ due to HR-HPVs that are not included in vaccines. The prevalence of infections with HPV 31, 33, 35 and 58 that contributed to CIN 2+ differed by race. In group A, African American (AA) women and current smokers were more likely to have CIN 2 (OR = 1.76, P = 0.032 and 1.79, P = 0.016, respectively) while in both groups of A and B, those with higher vitamin B12 were less likely to have similar lesions (OR = 0.62, P = 0.036 and 0.45, P = 0.035, respectively). We identified vitamin B12 status and smoking as independent modifiable factors and ethnicity as a factor that needs attention to reduce the risk of developing CIN 2+ in the post vaccination era. Continuation of tailored screening programs combined with non-vaccine-based approaches are needed to manage the residual risk of developing HPV-related CIN 2+ and CC in vaccinated women.

Retracted: Expression of GMFB in High-Grade Cervical Intraepithelial Neoplasia and Its Role in Cervical Cancer.

[This retracts the article DOI: 10.1155/2022/7784921.].

Editorial

Editorial

Accuracy of visual inspection, cytology and colposcopy in the diagnosis of high-grade cervical intraepithelial neoplasia

Introduction: Cervical cancer is still one of the leading causes of cancer and mortality in women, especially in low- and middle-income countries. Normally, the prevention of its occurrence is done through efficient screening and treatment programs for high-grade epithelial lesions, which are pre-malignant lesions. Cheaper diagnostic techniques ensure greater access to women, which can prevent a large number of cancer cases worldwide. Objective:The aim of the study was to evaluate the accuracy of visual inspection either with acetic acid or with Lugol’s iodine, cervical cytology and colposcopy in the diagnosis of cervical intraepithelial neoplasia 2 and 3. Methods: This is a study of diagnostic accuracy. We evaluated 115 women with high-grade squamous intraepithelial lesion confirmed by biopsy, 54 with cervical intraepithelial neoplasia 2 and 61 with cervical intraepithelial neoplasia 3, from January 2016 to December 2018 at the Lower Genital Tract Pathology and Colposcopy Service of the Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. A comparative analysis of the visual inspection, Pap smear and colposcopy diagnostic methods was performed. Results: The average age was 33.1 years (standard deviation=9.83) for cervical intraepithelial neoplasia 2 cases and 35.2 years (standard deviation=7.97) for cervical intraepithelial neoplasia 3. In the cervical intraepithelial neoplasia 2 group, visual inspection tests were positive for high-grade squamous intraepithelial lesion in 98.1% of the cases with acetic acid and 94.4% with Lugol’s iodine. Colposcopy identified a probable high-grade squamous intraepithelial lesion in 94.4% of the cases, while cytology only in 42.6%. In the cervical intraepithelial neoplasia 3 group, the visual inspection tests were positive for high-grade squamous intraepithelial lesion in 91.8% of the cases with acetic acid and 95.1% with Lugol’s iodine. Colposcopy identified a probable high-grade squamous intraepithelial lesion in 93.5% of the cases, while cytology in 65.6%. Conclusion: Visual inspection with acetic acid and Lugol’s iodine, and colposcopy test were more accurate for the diagnosis of cervical intraepithelial neoplasia 2 and 3 than through cytopathology.

High-Intensity Focused Ultrasound for Patients With Cervical Intraepithelial Neoplasia 2/3: A Prospective One-Arm Study.

The aim of this study was to ascertain the safety of high-intensity focused ultrasound (HIFU) for high-grade cervical intraepithelial neoplasia grade 2/3 (CIN 2/3) in patients with fertility requirements. This was a prospective one-arm study. Consecutive CIN 2/3 patients diagnosed with histopathology were screened, enrolled and treated from September 2019 to September 2020 in the Affiliated Hospital of North Sichuan Medical College. All patients were treated with a combination of HIFU and antiviral treatment with REBACIN. The scheduled follow-up visits were 1 week, 1 mo, 3 mo, 6 mo and 12 mo after surgery. The primary outcomes included cure and human papillomavirus clearance rates. We screened 287 consecutive CIN 2/3 patients in our hospital, 29 of whom were enrolled and treated in this study. The cure rate reached 82.8% at 7 mo after treatment and 96.6% within 1 y. The HPV-negative rate reached 72.4% (21/29) around 6 mo after treatment, with mild side effects during and after the procedure. Our study suggests that in CIN 2/3 study participants with fertility requirements, HIFU+REBACIN therapy is a safe and effective therapeutic option with a high cure rate, HPV clearance and few side effects.

Predictive value of HPV genotyping for recurrence of CIN2−3 in women treated by LEEP with negative resection margins

The aim of our study was to determine whether the HPV genotype identified by the HPV DNA chip (HDC) test could predict the recurrence of high-grade cervical intraepithelial neoplasia (CIN2–3) in women who had undergone a loop electrosurgical excision procedure (LEEP) and had negative margins. We analyzed the data of 1021 women with CIN2–3 treated by LEEP where histology confirmed negative resection margins. The women were followed up with HDC and endocervical cytology tests at 3, 6, 9, 12, 18 and 24 months during the first 2 years and annually thereafter. Among the 1021 patients, the pre-LEEP HDC test was positive for 992 (97.2%). A total of 90 (8.8%) patients experienced recurrence of CIN2–3 and the post-LEEP follow-up HDC tests were positive, thus demonstrating a persistent high-risk HPV infection of the same genotype, which showed a sensitivity and negative predictive value of 100%in predicting recurrence. We also examined the correlation between pre-LEEP high-risk HPV genotypes and recurrence. The most common subtypes were HPV16, HPV18 and HPV31. Persistence of HPV18 had the highest risk of recurrence of CIN2–3 (p < 0.05). Our study suggests that type-specific persistent high-risk HPV infection, particularly the HPV18 subtype, is a significant predictor of recurrence in patients with negative resection margins in the LEEP specimens. Thus, these patients require careful monitoring, and gynecologic oncologists should conduct short-term follow-up tests.

Human papillomavirus prevalence, persistence and cervical dysplasia in females with cystic fibrosis

BackgroundA higher risk of human papillomavirus (HPV)-related cervical intra-epithelial neoplasia (CIN) is suspected among females with cystic fibrosis (CF). MethodsWe conducted a single center prospective cohort study among females attending the Lyon adult CF center. We performed a cervical cytology (Hologic Thinprep®) and HPV testing with genotyping (Clinical Arrays Papillomavirus; Genomica, enabling 35 genotype detection, 20 of which are high-risk (HR-HPV)) at inclusion. We followed all females with positive HPV tests at 6, 12 and 24 months to evaluate HPV persistence, and performed a colposcopy in cases of abnormal cytology. ResultsWe included eighty-five participants, 18 (21%) of whom were lung-transplanted. The mean age at inclusion was 31.9 (range 18-59) years. The prevalence of HPV (all types) was 31.8%. HR-HPV was found in 25.9% of the whole cohort, 44.4% of transplanted patients, and 20.1% of nontransplanted patients. Genotype-specific HR-HPV persistence at 12 months was 43.5% among transplanted and 34.6% among nontransplanted patients. Overall, 17.6% (15/85) of females had an abnormal cytology: 44.4% (8/18) among transplanted and 10.4% (7/67) among nontransplanted patients. CIN was identified in 12 (14.1%) patients (6 low-grade, 6 high-grade). High-grade CIN developed in 4 nontransplanted patients. ConclusionTransplanted females had high HR-HPV, abnormal cervical cytology and CIN prevalence rates compared to large published cohorts in the general non-CF population. Although HR-HPV prevalence and persistence were globally not significantly different in nontransplanted females compared to the general population, we reported high frequencies of abnormal cytology and CIN. Cervical cancer screening and prevention should be promoted among females with CF.

Effect of Human Papillomavirus Subtype on the Rate of Positive Surgical Margin After Cervical Conization

Objective. Human papillomavirus (HPV) infection is a risk factor for cervical carcinoma. Over 100 types of HPV have been identified. The excisional procedures are recommended for women with high-grade cervical intraepithelial neoplasia. Surgical margin status is an important predictor of the risk of relapse. The aim of the current study was to evaluate whether HPV genotype is a predictive factor of positive surgical margin after cervical cone excision. Materials and Methods. The records of 448 HPV-infected patients who underwent loop electrosurgical excision or cold knife conization at a tertiary gynecological cancer center were retrospectively reviewed. The patients were divided into 6 groups according to HPV positivity: HPV 16 only, HPV 18 only, HPV 16/18, other high-risk HPV (hrHPV), HPV 16/hrHPV, and HPV 18/hrHPV. Results. There was no significant difference between the HPV groups in terms of age, parity, menopausal status, endocervical canal involvement, conization method, and the rates of positive margin (P = .15, P = .49, P = .07, P = .20, P = .24, P = .39, respectively). Conclusion. The results show that HPV subtypes might not be associated with endocervical canal involvement and the rates of positive margin. In addition, margin status was not related to the conization method and the number of excised cervical tissue.

Risks and treatment for recurrent intraepithelial cervical lesions

Background. Persistently high incidence of cervical cancer in Russia and significant number of cases detected in the late stages necessitate the improvement of secondary prophylaxis of this disorder.Aim. To assess risk factors for recurrent high-grade cervical intraepithelial neoplasia (CIN2+) (high grade squamous intraepithelial lesions, HSIL) after cervical conization.Materials and methods. This study included 62 patients with recurrent HSIL treated in Novosibirsk Regional Clinical Oncology Dispensary, E. N. Meshalkin National Medical Research Center, “Zdorovye” LLC, “Avismed” LLC, Tomsk National Research Medical Center of the Russian Academy of Sciences, and Federal Research and Clinical Center for Specialized Medical Care and Medical Technologies, Federal Biomedical Agency of the Russian Federation in 2017–2021. We analyzed patients’ human papillomavirus (HPV) status, performed repeated examination of excised tissue specimens to evaluate the severity of lesions and resection margins, as well as immunohistochemical examinations. We found that mean time to cytologically confirmed recurrent HSIL was 16.0 ± 5.6 months. All patients were HPV-positive. Repeated histological examination demonstrated that 18 samples had positive resection margins or endocervical crypt involv ement. Fifty-seven samples had positive staining for p16 at immunohistochemical examination; 46 samples had Ki-67 >30 %, which indicated high risk of recurrence. Treatment of patients with recurrent HSIL included repeated excision up to healthy cervical tissues, followed by intravaginal therapy with Cervicon-DIM 100 mg twice a day (for 3 months). Follow-up examinations after 18.0 ± 6.2 months on average showed no HPV persistence and no HSIL recurrence.Conclusion. Endocervical crypt involvement along the primary resection margin, underestimated severity and depth of lesions (at the first surgery), and persistence of HPV infection are the main risk factors for recurrent cervical dysplasia or carcinoma in situ. Combination treatment that includes additional excision with a subsequent course of Cervicon-DIM is sufficient and effective.

Can portable Colposcopes Replace Standard-of-care Colposcopes? A Crossover Trial of Two Portable Colposcopes with a Standard-of-Care Video Colposcope

Screen positive women need to be triaged by colposcopy which is a major challenge in low-middle income countries. Portable colposcopes may overcome many challenges, reduce referrals and enable a single visit approach. This study assessed the performance of portable colposcopes and potential to reduce referral. This crossover randomised study enrolled women aged 25 to 65 years with abnormal screening result or cervical symptoms. All women underwent visual inspection with acetic acid (VIA), HPV test, colposcopy with two portable colposcopes (Gynocular®, Gynius, Sweden, and Pocket® transvaginal colposcope, Duke University, NC, USA) and a standard video colposcope, and biopsy. Colposcopic Swede score agreement between portable and video colposcopes, as well as agreement of Swede score with histology were calculated for each device. The potential impact of portable colposcopes in a single visit approach was assessed based on the final diagnosis. Among 250 subjects, 27(10.80%) had high-grade cervical intraepithelial neoplasia (CIN2+) lesions. Swede scores for Pocket and Gynocular colposcopes were similar to video colposcope in 248 (99.20%) and 247 (98.80%) subjects, respectively (agreement scores 0.9969 and 0.9954, respectively). At a Swede score cut-off of ≥5, all three devices had identical sensitivity, specificity, positive and negative predictive value of 96.30%, 92.30%, 60.50% and 99.50,. Ablative treatment offered at field setting would result in optimal treatment in 52.0% and 85.1% cases when screened with VIA and HPV test respectively; using Pocket colposcope could improve this to 94.0% and 95.9%, respectively. Overtreatment and referral rates reduced from 46.8% and 12.4% to 4.8% and 6.0%, respectively, when VIA test is followed by triage with pocket colposcope. These outcomes were comparable to screening with HPV followed by colposcopy triage. Pocket colposcope performed comparably to the video colposcope. Used by healthcare providers in the field setting, they can augment the results of VIA significantly.

Evaluation of co-testing with cytology and human papillomavirus testing in cervical screening

Cervical screening is increasingly switching to human papillomavirus (HPV) testing. In many settings, the switch has involved one or several co-tests (testing using both cytology and HPV) in the screening guidelines, to ensure safety. When Sweden switched to HPV testing in 2015 the guidelines included a co-test at age 41.To evaluate the effect of co-testing, we identified all 208,701 women resident in Sweden who in 2019 were 40–42 years old and thus eligible for co-testing. All cervical samples, the results of the test and of the subsequent biopsies were identified in the Swedish National Cervical Screening Registry. Out of the 10,643 women with co-testing in screening, there were 197 women with a subsequent biopsy with high-grade cervical neoplasia or worse (CIN2+). Among these 197 women, 189 had a screening test positive for both HPV and cytology, 6 women were HPV+/Cyt- and 2 women were HPV-/Cyt+. There were 7115 women with a co-test outside of the screening program. Among these, 325 women had a CIN2+ in histopathology, 290 were double positive, 13 women were cyt+/HPV-, and 11 women each were HPV+/cyt- and HPV-/Cyt-. In summary, the additional yield of CIN2+ with co-testing was 2 cases per 10,643 women as compared with 195/10,643 CIN2+ cases detected with HPV screening alone. However, for cervical samples taken outside the screening program (e.g. taken on a clinical indication) there was an increased yield (314 CIN2+ cases detected with co-testing as compared to 301 cases with HPV screening).

Widening the offer of human papillomavirus self-sampling to all women eligible for cervical screening: Make haste slowly.

Self-collection of samples for human papillomavirus (HPV) testing has the potential to increase the uptake of cervical screening among underscreened women and will likely form a crucial part of the WHO's strategy to eliminate cervical cancer by 2030. In high-income countries with long-standing, organised cervical screening programmes, self-collection is increasingly becoming available as a routine offer for women regardless of their screening histories, including under- and well-screened women. For these contexts, a validated microsimulation model determined that adding self-collection to clinician collection is likely to be cost-effective on the condition that it meets specific thresholds relating to (1) uptake and (2) sensitivity for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We used these thresholds to review the 'early-adopter' programme-level evidence with a mind to determine how well and how consistently they were being met. The available evidence suggested some risk to overall programme performance in the situation where low uptake among underscreened women was accompanied by a high rate of substituting clinician sampling with self-collection among well-screened women. Risk was further compounded in a situation where the slightly reduced sensitivity of self-sampling vs clinician sampling for the detection of CIN2+ was accompanied with lack of adherence to a follow-up triage test that required a clinician sample. To support real-world programmes on their pathways toward implementation and to avoid HPV self-collection being introduced as a screening measure in good faith but with counterproductive consequences, we conclude by identifying a range of mitigations and areas worthy of research prioritisation.

Should attention be paid to the cone depth in the fully visible transformation zone? Retrospective analysis of 517 patients with cervical intraepithelial neoplasia grade 3.

The predictors of positive endocervical margin (EM) and a cone-depth cutoff value are not established in the fully visible transformation zone (TZ). The present study aimed to assess the independent variables associated with positive EM in women with high-grade cervical intraepithelial neoplasia (CIN) and fully visible TZ. The current investigation was a retrospective study including women with fully visible TZ and CIN 3 cone histology between 2014 and 2019. The sample was divided into women with positive versus those with negative EM. Univariate and multivariate analyses were performed. Finally, receiver operating characteristic curve analysis was also used. A total of 123 of 517 women (23.8%) showed positive EM at conization. Multivariate analysis found a positive association with type 2 TZ (odds ratio [OR], 2.17 [95% confidence interval (CI), 1.19-3.94]) and lesion extension ≥2 cervical quadrants (OR, 35.57 [95% CI, 17.96-70.45]). Cone depth was inversely related to positive EM (OR, 0.71 [95% CI, 0.63-0.80]). In women with type 2 TZ and lesion extension ≥2 cervical quadrants, the cutoff value was achieved at 8-mm cone depth (area under the curve, 0.79 [95% CI, 0.67-0.90]). In women with high-grade CIN and fully visible TZ undergoing conization, the lesion extension and the TZ subtype (1 or 2) should be considered. A no less than 9-mm cone depth provided a fair predictive value in achieving free EM.

Performance of HPV testing, Pap smear and VIA in women attending cervical cancer screening in Kilimanjaro region, Northern Tanzania: a cross-sectional study nested in a cohort

ObjectiveThere is a concern about performance of the screening approaches, where information on the quality of novel and affordable screening approaches that will perform well in remote areas is warranted....