cervical intraepithelial neoplasia grade
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Author(s):  
Kun Fu ◽  
Ming Lei ◽  
Li-Sha Wu ◽  
Jing-Cheng Shi ◽  
Si-Yu Yang ◽  
...  

Abstract Background The colposcopy-conization inconsistency is common in women with cervical intraepithelial neoplasia grade 3 (CIN3). No adequate method has been reported to identify the final pathology of conization. In this study, we explored the ability of PAX1 and ZNF582 methylation to predict the pathological outcome of conization in advance. Methods This was a multicenter study and included 277 histologically confirmed CIN3 women who underwent cold knife conization (CKC) from January 2019 to December 2020. The methylation levels of PAX1 (PAX1m) and ZNF582 (ZNF582 m) were determined by quantitative methylation specific PCR (qMSP) and expressed in ΔCp. Receiver-operating characteristic (ROC) curves were used to evaluate predictive accuracy. Results The final pathological results in 48 (17.33%) patients were inflammation or low-grade squamous intraepithelial lesion (LSIL), 190 (68.59%) were high grade squamous intraepithelial lesion (HSIL) and 39 (14.08%) were squamous cervical cancer (SCC). PAX1 m and ZNF582 m increased as lesions progressed from inflammation/LSIL, HSIL to SCC. PAX1 and ZNF582 methylation yielded better prediction performance compared to common screening strategies, whether individually or combined. ΔCpZNF582 ≥19.18). A 6.53-fold increase in SCC risk was observed in patients with elevated ZNF582 methylation (ΔCpZNF582 < 7.09). Conclusion DNA Methylation would be an alternative screening method to triage and predict the final outcome of conization of the CIN3 cases.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Teruhiko Terasawa ◽  
Satoyo Hosono ◽  
Seiju Sasaki ◽  
Keika Hoshi ◽  
Yuri Hamashima ◽  
...  

AbstractTo compare all available accuracy data on screening strategies for identifying cervical intraepithelial neoplasia grade ≥ 2 in healthy asymptomatic women, we performed a systematic review and network meta-analysis. MEDLINE and EMBASE were searched up to October 2020 for paired-design studies of cytology and testing for high-risk genotypes of human papillomavirus (hrHPV). The methods used included a duplicate assessment of eligibility, double extraction of quantitative data, validity assessment, random-effects network meta-analysis of test accuracy, and GRADE rating. Twenty-seven prospective studies (185,269 subjects) were included. The combination of cytology (atypical squamous cells of undetermined significance or higher grades) and hrHPV testing (excepting genotyping for HPV 16 or 18 [HPV16/18]) with the either-positive criterion (OR rule) was the most sensitive/least specific, whereas the same combination with the both-positive criterion (AND rule) was the most specific/least sensitive. Compared with standalone cytology, non-HPV16/18 hrHPV assays were more sensitive/less specific. Two algorithms proposed for primary cytological testing or primary hrHPV testing were ranked in the middle as more sensitive/less specific than standalone cytology and the AND rule combinations but more specific/less sensitive than standalone hrHPV testing and the OR rule combination. Further research is needed to assess these results in population-relevant outcomes at the program level.


2021 ◽  
pp. 1-12
Author(s):  
Laura Gilbert ◽  
Sam Ratnam ◽  
Dan Jang ◽  
Reza Alaghehbandan ◽  
Miranda Schell ◽  
...  

OBJECTIVES & METHODS: CINtec PLUS and cobas HPV tests were compared for triaging patients referred to colposcopy with a history of LSIL cytology in a 2-year prospective study. Cervical specimens were tested once at enrollment, and test positivity rates determined. Test performance was ascertained with cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3 or worse (CIN3+) serving as clinical endpoints. RESULTS: In all ages, (19–76 years, n= 598), 44.3% tested CINtec PLUS positive vs. 55.4% HPV positive (p< 0.001). To detect CIN2+ (n= 99) CINtec PLUS was 81.8% sensitive vs. 93.9% for HPV testing (p= 0.009); genotype 16/18-specific sensitivity was 46.5%. Specificity was 52.9% vs. 36.6%, respectively (p< 0.001). In all ages, to detect CIN3+ (n= 44), sensitivity was 93.2% for both tests; genotype 16/18-specific sensitivity was 52.3%. Specificity was 48.4% for CINtec PLUS vs. 31.1% for HPV testing (p< 0.001). In patients < 30 years, CINtec was 91.7% sensitive vs 95.8% for HPV testing (p= 0.549). CONCLUSIONS: CINtec PLUS or cobas HPV test could serve as a predictor of CIN3+ with high sensitivity in patients referred to colposcopy with a history of LSIL regardless of age while significantly reducing the number of LSIL referral patients requiring further investigations and follow-up in colposcopy clinics.


2021 ◽  
Vol 23 (1) ◽  
pp. 373
Author(s):  
Irene Tveiterås Øvestad ◽  
Birgit Engesæter ◽  
Mari Kyllesø Halle ◽  
Saleha Akbari ◽  
Beatrix Bicskei ◽  
...  

Implementation of high-risk human papilloma virus (HPV) screening and the increasing proportion of HPV vaccinated women in the screening program will reduce the percentage of HPV positive women with oncogenic potential. In search of more specific markers to identify women with high risk of cancer development, we used RNA sequencing to compare the transcriptomic immune-profile of 13 lesions with cervical intraepithelial neoplasia grade 3 (CIN3) or adenocarcinoma in situ (AIS) and 14 normal biopsies from women with detected HPV infections. In CIN3/AIS lesions as compared to normal tissue, 27 differential expressed genes were identified. Transcriptomic analysis revealed significantly higher expression of a number of genes related to proliferation, (CDKN2A, MELK, CDK1, MKI67, CCNB2, BUB1, FOXM1, CDKN3), but significantly lower expression of genes related to a favorable immune response (NCAM1, ARG1, CD160, IL18, CX3CL1). Compared to the RNA sequencing results, good correlation was achieved with relative quantitative PCR analysis for NCAM1 and CDKN2A. Quantification of NCAM1 positive cells with immunohistochemistry showed epithelial reduction of NCAM1 in CIN3/AIS lesions. In conclusion, NCAM1 and CDKN2A are two promising candidates to distinguish whether women are at high risk of developing cervical cancer and in need of frequent follow-up.


2021 ◽  
pp. 1711-1721
Author(s):  
Emma R. Allanson ◽  
Natacha Phoolcharoen ◽  
Mila P. Salcedo ◽  
Bryan Fellman ◽  
Kathleen M. Schmeler

PURPOSE Smartphones are used in cervical screening for visual inspection after acetic acid or Lugol's iodine (VIA/VILI) application to capture and share images to improve the sensitivity and interobserver variability of VIA/VILI. We undertook a systematic review and meta-analysis assessing the diagnostic accuracy of smartphone images of the cervix at the time of VIA/VILI (termed S-VIA) in the detection of precancerous lesions in women undergoing cervical screening. METHODS This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies from January 1, 2010, to June 30, 2020, were assessed. MEDLINE/PubMed, Embase, CINAHL, Cochrane, and LILACS were searched. Cohort and cross-sectional studies were considered. S-VIA was compared with the reference standard of histopathology. We excluded studies where additional technology was added to the smartphone including artificial intelligence, enhanced visual assessment, and other algorithms to automatically diagnose precancerous lesions. The primary outcome was the accuracy of S-VIA for the diagnosis of cervical intraepithelial neoplasia grade 2 or greater (CIN 2+). Data were extracted, and we plotted the sensitivity, specificity, negative predictive value, and positive predictive value of S-VIA using forest plots. This study was prospectively registered with The International Prospective Register of Systematic Reviews:CRD42020204024. RESULTS Six thousand three studies were screened, 71 full texts assessed, and eight studies met criteria for inclusion, with six included in the final meta-analysis. The sensitivity of S-VIA for the diagnosis of CIN 2+ was 74.56% (95% CI, 70.16 to 78.95; I2 61.30%), specificity was 61.75% (95% CI, 56.35 to 67.15; I2 95.00%), negative predictive value was 93.71% (95% CI, 92.81 to 94.61; I2 0%), and positive predictive value was 26.97% (95% CI, 24.13 to 29.81; I2 61.3%). CONCLUSION Our results suggest that S-VIA has accuracy in the detection of CIN 2+ and may provide additional support to health care providers delivering care in low-resource settings.


2021 ◽  
pp. 89-94
Author(s):  
Y.B. Yakymchuk

Research objective: the use of an immunomodulator III generation with a wide range of action (muramyl peptide drug Liastenum) to increase the effectiveness of treatment of cervical intraepithelial neoplasia grade I associated with human papilloma virus (HPV) and to reduce the recurrence of cervical pathology.Materials and methods. The study included 60 women with histologically confirmed cervical intraepithelial neoplasia associated with highly oncogenic HPV. The mean age of patients was 25.92 ± 0.61 years. The first group included 30 women who received traditional treatment, the second group included 30 women who additional received Liastenum 0.002 g intramuscularly 1 time per day, 5 injections per course, after that patients took 1 tablets Liastenum twice a day for 20 days.Traditional treatment included antibiotic therapy (doxycycline monohydrate), metronidazole, nystatin in standard dosage. Patients with herpes viruses received valaciclovir 500 mg twice/day for 5 days. Evaluation of treatment efficacy was performed at 6 and 12 months with co-testing, fluid cytology, HPV quantification, and colposcopy.Results. There was a significant decrease in the exposure level of highly oncogenic HPV in the second group compared to the first: after 12 months in the first group HPV was not detected in 2 women (6.67%), and in the second group HPV was no detected in 17 women (56.67%) (p < 0.05). Improvement of the colposcopic picture occurred in 70% of patients in the second group, and in 12 (40.0%) of patients colposcopic conclusion on the Swedish scale was less than 3 points after 12 months of observation. Only 8 (26.67%) women received improvement of the colposcopic picture with a score of 3 points on the Swedish scale in the first group, which was significantly different from the second group (p < 0.05).Conclusions. Advanced therapy with muramyl peptide Liastenum in the treatment of cervix for 12 months can increase the effectiveness of HPV elimination, improves the colposcopic picture by reducing the area of cervical lesions and normalized cytological picture in 70% of patients with cervical intraepithelial neoplasia grade I.


Author(s):  
O. P. Vinogradova ◽  
N. A. Andreeva ◽  
O. V. Epifanova

Introduction. The viral antigenic load can influence the nature of the infectious response, leading to elimination of the virus or to chronicity of the process, and in some cases to the progressive course of the disease. The aim of the study was to investigate the relationship between the types of viral load of human papillomavirus and the age of a patient with cervical cervical intraepithelial neoplasia grade I. Material and methods. 86 patients with cervical papillomavirus-induced cervical intraepithelial neoplasia grade I by liquid oncocytology were examined. The frequency of human papillomavirus genotypes of high carcinogenic risk in this group of women was analyzed taking into account the viral load by polymerase chain reaction with real-time hybridization-fluorescence detection. The correlation between the viral load of the human papillomavirus and the age of the patient with further prediction of the regression or progression of cervical pathology was studied. Results. This study found that female patients under 30 years of age with cervical intraepithelial neoplasia grade I associated with papillomavirus infection showed a decrease in viral load after 12 months of follow-up in 30.2%, and in patients with cervical intraepithelial neoplasia grade I of older age — in 9.3%. Discussion. The management tactics for grade I cervical intraepithelial neoplasia associated with papillomavirus infection depends largely on the age of the patients and the degree of viral load. In young patients with immediate reproductive plans, a wait-and-see approach with dynamic observation for 12 months without drug therapy is possible in view of the probable spontaneous elimination of the human papillomavirus within a year. The results of the study suggest a higher rate of human papillomavirus elimination in cervical intraepithelial neoplasia grade I in women under 30 years of age. Conclusion. In cervical intraepithelial neoplasia of degree I in women under 40, infection with several types of the human papilloma virus (16, 18, 31, 51) with a clinically significant viral load (over 4.69±0.07 HPV per 100,000 cells) was found most frequently. In the group of the older reproductive age (40-49 years old), HPV HCC is less frequent in 6.90%. And the predominant role belongs to type 16, which was spread in 69.7% of cases.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S505-S506
Author(s):  
Leahanne Giffin ◽  
Yuwei Zhu ◽  
Manideepthi Pemmaraju ◽  
Sheelah Blankenship ◽  
Emmanuel Sackey ◽  
...  

Abstract Background Women living with HIV (WLWH) experience high rates of human papillomavirus (HPV) infection and increased risk of cervical cancer. High-risk HPV (HR-HPV) types 16/18 cause most cervical precancers and cancers in women with and without HIV. However, contributions of other HR-HPV types to cervical disease among WLWH are not fully understood. We compared CIN2+ cases (cervical intraepithelial neoplasia grade 2 or higher or adenocarcinoma in situ) and the association between non-16/18 HPV types among women with and without HIV. Methods Davidson County, Tennessee, women aged 18-39 years with CIN2+ diagnosed between 2008-2016 with HPV genotyping were included. HIV status, demographics, and histology were abstracted from medical records. Neighborhood-level socioeconomic factors were derived from Integrated Public Use Microdata Series. Archived cervical tissue was tested for 37 HPV types to define CIN2+ cases negative for HPV 16/18, regardless of presence of other HR-HPV strains. Characteristics of women with CIN2+ and HPV typing patterns were compared between women with and without HIV using Wilcoxon and Chi-square tests. Logistic regression assessed the association of non-16/18 HPV types and HIV infection, adjusting for age, race, calendar year, insurance, HPV vaccination, and neighborhood socioeconomic factors (selected a priori). Results Among 2,116 women included, 1,093 (52%) had neither HPV16 nor HPV18. Compared to women without HIV, the 27 WLWH included were more likely to be &gt;30 years of age, Black race, and live in neighborhoods with higher measures of poverty (Table 1). HPV types did not statistically differ by HIV status, though WLWH had a higher number of HR-HPV types present (Table 2). HIV infection was not significantly associated with non-16/18 HPV type after adjusting for confounders (adjusted OR 0.86 [95%CI: 0.4-1.88]). Conclusion Among women with CIN2+, HIV infection was not significantly associated with non-16/18 HPV types. However, WLWH had a higher number of high-risk HPV types detected. Our study was limited by the small number of WLWH included. Disclosures All Authors: No reported disclosures


Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2012
Author(s):  
Martyna Trzeszcz ◽  
Maciej Mazurec ◽  
Robert Jach ◽  
Karolina Mazurec ◽  
Zofia Jach ◽  
...  

Recently, cervical cancer rates elevation has been noted in women aged 20–39 years in regions with a very high human development index (HDI). The onset of cancer elevation rates is observed in the age range of 25–29 years, which should necessitate effective precancer screening in younger age groups, including those <25 years. From 30.066 liquid-based screening tests results (n = 30.066), 3849 liquid-based cytology, 1321 high-risk human papillomavirus (HRHPV) and 316 p16/Ki67 performed in women <30 years were selected. Performance characteristics were calculated for three screening models: primary HRHPV with p16/Ki67 triage, primary cytology with reflex HPV and primary cytology alone. Primary HRHPV with p16/Ki67 triage was significantly more sensitive in high-grade squamous intraepithelial lesion quantified with cervical intraepithelial neoplasia grade 2 or worse [HSIL(CIN2+)] detection than cytology with reflex HRHPV and cytology alone (83.3% vs. 70.8%/45.8%) and had significantly higher diagnostic predictive values (PPV:29.4%/21.3%/22.9%; NPV:91.7%/82.9%/82.2%, respectively at CIN2+ threshold). The number of colposcopies per HSIL(CIN2+) detection indices was 3.4, 4.7 and 4.4, respectively. Primary HPV testing in women <30 years with p16/Ki67 triage of HPV-positive cases might be an effective cervical cancer screening strategy for HSIL(CIN2+) detection with superior diagnostic performance when compared with primary cytology-based models. Women <25 years might also benefit from an introduction to a more sensitive screening approach.


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