Cervical Intraepithelial Neoplasia In Women Research Articles

Distribution and Severity of Cervical Intraepithelial Neoplasia in Women With Different Human Papillomavirus: An Analysis From Liaoning Province of Northeastern China.

Persistent infection with high-risk human papillomavirus (HPV) is a key contributor to cervical intraepithelial neoplasia (CIN), but the relation between high-risk HPV genotypes and the location of CIN lesions remains unclear. The aims of this study were to investigate the most frequent biopsy site of CIN lesions in women with different HPV infection and to analyze the biopsy times, CIN frequency, and the clustering of CIN frequency based on 12-o'clock sites and cervical quadrant locations. We conducted a retrospective study of HPV detection and genotyping at the virology department of our hospital. Colposcopy exams were performed by specialists according to a standardized protocol, and all visually abnormal areas were further biopsied. Pearson chi-squared tests and cluster analyses were implemented to analyze the data. Among 1,381 women enrolled in this study, 933 cases infected with HPV. HPV16, HPV58, and HPV18 were the most common genotypes. The most frequent biopsy site was the 6 o'clock position. The highest frequency of high-grade CIN findings in single-genotype HPV groups was the 6 o'clock position and that for multiple-genotype HPV group was the 12 o'clock location. All CIN clusters were found in the 6 and 12 o'clock biopsy sites, except in the HPV18 group. Quadrant 2 and 4 were clustered in most groups. The 6 and 12 o'clock sites in cervical quadrant 2 and 4 should be targeted during cervical biopsy procedures. These findings can provide clinicians with specific recommendations on the optimal site for CIN biopsy when considering the HPV genotype.

MODERN VIEWS OF THE PROGRESSION OF CERVICAL NEOPLASIA AFTER DESTRUCTIVE TREATMENTS FOR CERVICAL DISEASES

Diagnosis of cervical intraepithelial neoplasia in women with a history of exocervix ablation is difficult due to the displacement of the junction of the squamous and prismatic epithelium into the cervical canal. Diagnostic significance in these cases belongs to the data of cytological examination of cells obtained with the help of a cyto-brush from the cervical canal. The diagnosis was clarified by coni biopsy. In 20 (17%) of the 70 women followed, CIN and cervical cancer were detected. Patients with ablation exocervixes have a history of developing intracervical neoplasias with the persistence of highly oncogenic types of HPV (human papillomavirus), so they need endocervix cytological control, viral load, and papillomavirus genotype annually as secondary prevention of cervical cancer.

The association between human papillomavirus infection, vaginal microecology, and cervical intraepithelial neoplasia in women from Xinjiang, China.

This study analyzes the relationship between human papillomavirus (HPV) infection, vaginal microecology, and cervical lesions to provide a basis for the prevention and treatment of cervical cancer (CC) in the Xinjiang region. Real-time quantitative PCR was used for HPV genotyping and viral load. The Gram staining and dry biochemical enzyme kit were utilized to diagnose vaginal secretions. The χ2 test and Logistic regression analysis were used for statistical analysis. The HPV infection rate among women in the Xinjiang region was 30.29%, of which the single HPV infection accounts for 77%. HPV16 and HPV52 were the main infection types. There was significant differences in the HPV infection rate and infection types among the Han, Uighur, Hui, and Kazakh ethnic groups. The viral load of HPV16 and HPV52 increases with the upgrade of cervical lesions. There were significant differences in vaginal microecology evaluation indicators H2O2, SNA, LE, GUS, trichomonas, clue cells, and lactobacilli among different ethnic groups. HPV negative patients with varying grades of cervical lesions exhibit a notable variance in H2O2 and LE, which is statistically significant. Single HPV infection and high viral load HPV significantly increase the risk of CC. This study indicates that HPV infection and vaginal microecology differ among ethnic groups, which have a strong correlation with the progression of CC, offering guidance on CC screening and interventions in the Xinjiang area.

Comparison of visual inspection of Cervix with acetic acid with conventional pap smear in the detection of colposcopic biopsy proved cervical intraepithelial neoplasia in women presenting in Tertiary Care Hospital

Comparison of visual inspection of Cervix with acetic acid with conventional pap smear in the detection of colposcopic biopsy proved cervical intraepithelial neoplasia in women presenting in Tertiary Care Hospital

Diagnostic Accuracy of p16INK4a/Ki-67 Dual Immunostaining for Detection of High-Grade Cervical Intraepithelial Neoplasia in Women Involved in Cervical Cancer Screening in Georgia.

Despite the widespread introduction of primary and secondary preventative measures, death rates for cervical cancer are still significantly high among females, especially in developing countries. Pap cytology and human papillomavirus-based screening often lead to unnecessary additional testing. The aim of this study is to analyze diagnostic accuracy of p16INK4a/Ki-67 dual immunostaining (DS) in cervical smear for identifying high-grade cervical intraepithelial neoplasia (CIN2+). We studied the diagnostic performance of p16INK4a/Ki-67 DS in cervical smear of those women, who enrolled in cervical cancer screening due to abnormal previous screening results and compared it with Pap test results in identifying CIN2+. The reference standard was histopathology results. p16INK4a/Ki-67 DS and Pap test results for 162 women and histopathology results for 29 women were available, respectively. In our study, sensitivity, specificity, positive predictive value, and negative predictive value of p16INK4a/Ki-67 DS, irrespective of the morphology of stained cells to detect CIN2+ were 100%, 89%, 85%, and 100% (p < 0.01), respectively. The diagnostic accuracy of p16INK4a/Ki-67 DS is superior to that of existing cervical screening tests in the detection of CIN2+. The findings of cervical cancer screening based on Pap cytology highlight the importance of assessing the cost-effectiveness of integrating p16INK4a/Ki-67 biomarkers in cervical cancer cytology. Furthermore, these findings emphasize the need to enhance support for preventive programs for cervical cancer in Georgia.

Cervical intraepithelial neoplasia in women with transformation zone type3: cervical biopsy versus large loop excision.

To compare the proportion of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) in cervical biopsies with that in large loop excision of the transformation zone (LLETZ) specimens in women aged ≥45 years with transformation zone type 3 (TZ3). Multicentre cross-sectional study. Three colposcopy clinics in the Central Denmark Region. Women aged ≥45 years referred to colposcopy as a result of a positive human papillomavirus (HPV) test and/or abnormal cytology and with TZ3 at colposcopy. Women had multiple biopsies taken and an LLETZ was performed. Histologically confirmed CIN2+ in biopsies compared with that in LLETZ specimens. Of 166 eligible women at colposcopy, 102 women with paired data from biopsies and LLETZ specimens were included for final analysis. The median age was 67.7 years (IQR 62.6-70.4 years), and most were postmenopausal (94.1%) and had undergone HPV-based screening (81.3%). The CIN2+ detection rate was significantly higher in LLETZ specimens than in biopsies (32.4% vs 14.7%, difference 17.7%, 95%CI 6.3-29.0%), resulting in more than half of CIN2+ cases being missed in biopsies (54.5%, 95%CI 36.4-71.9%). The overall agreement between biopsies and LLETZ was 82.4% (95%CI 73.6-89.2%). CIN2+ detection is underestimated in women aged ≥45 years with TZ3 if detection relies on the results of biopsies alone. To reduce the risk of underdiagnosis and overtreatment, future studies should explore the use of new biomarkers for risk stratification to improve discrimination between women at increased risk of CIN2+ who need to undergo LLETZ and women who may undergo follow-up.

Diagnostics of the severity of cervical intraepithelial neoplasia in women with infertility in the presence of papillomavirus infection

Diagnostics of the severity of cervical intraepithelial neoplasia in women with infertility in the presence of papillomavirus infection

Diagnostics of the severity of cervical intraepithelial neoplasia in women with infertility in the presence of papillomavirus infection

Diagnostics of the severity of cervical intraepithelial neoplasia in women with infertility in the presence of papillomavirus infection

Performance of the Swede score to predict cervical intraepithelial neoplasia in women with HIV-1 in Johannesburg, South Africa.

To evaluate the performance of the Swede score to detect cervical intraepithelial neoplasia (CIN) in women with HIV-1 in Johannesburg, South Africa. A cross-sectional study using secondary data analysis from the HPV in Africa Research Partnership (HARP) study that compared the performance of three different screening tests to detect CIN. Colposcopy was performed on any woman who screened positive and findings were recorded using the Swede score. A biopsy of any lesion and a four-quadrant biopsy was taken. The score was evaluated against a histological diagnosis of >CIN1. The sensistivity, specificity, PPV and NPV for each score was calculated. Median age and CD4+ count of the 576 women eligible from the Johannesburg cohort was 34years (IQR, 30-39) and 427cells/mm3 (IQR, 323-579), respectively. Almost two-thirds (64%) were on ART and about 21% had CIN2+ on histology. A Swede score of 5 or greater had the best combination of sensitivity and specificity for CIN2+ with an AUC of 0.72 (95% CI, 0.68-0.76) corresponding to a sensitivity of 72.1 (95% CI, 63.5-79.6) and specificity of 71.8 (95% CI, 67.4-75.9). The Swede score can assist in determining whether women with HIV/AIDS should have treatment at the first colposcopy visit versus those who may be followed up, thereby individualizing treatment.

Cytokine profile in grade II cervical intraepithelial neoplasia in women with papillomavirus infection

Cytokine profile in grade II cervical intraepithelial neoplasia in women with papillomavirus infection

Corrigendum to "Cervical intraepithelial neoplasia in women who had vaccination against HPV" [Int J Gynecol Obstet 147(2019) 233-237.

Corrigendum to "Cervical intraepithelial neoplasia in women who had vaccination against HPV" [Int J Gynecol Obstet 147(2019) 233-237.

Cervical intraepithelial neoplasia in women who had vaccination against HPV.

To investigate the characteristics of women developing cervical intraepithelial neoplasia who had had a vaccination against human papillomavirus (HPV). A retrospective cohort study was carried out of women diagnosed with moderate or severe cervical dysplasia (CIN2+) in four Italian centers between 2015 and2017. All women included had had previous bivalent or quadrivalent vaccination against HPV. The present study included 43 patients affected by CIN2+. The median age was 28 (range, 21-41) years. Ten (23.3%) patients did not have a diagnosis of specific HPV type(s) involved: high-risk HPV was detected in 7 (16.3%) women while HPV testing was negative in 3 (6.9%) women. Lesions related to HPV16 were found in two patients. HPV types covered by nonavalent vaccination were diagnosed in 27/33 (81.8%) women. HPV types not covered by nonavalent vaccination were diagnosed in 6 (18.2%) women. Co-infections are most commonly detected in women with HPVs other than those included in the nonavalent vaccination (P=0.024). Cervical dysplasia occurring after HPV vaccination is a rare condition. Theoretically, nonavalent vaccination should improve protection against more than 80% of HPV-related lesions compared to other vaccines.

Rates of regression of cervical dysplasia between initial biopsy and excisional procedure in routine clinical practice.

To determine rates and factors associated with regression of cervical intraepithelial neoplasia (CIN) 2 + between colposcopic biopsy and therapeutic excisional procedure in standard practice. A retrospective chart review was performed for women undergoing a cervical excisional procedure for CIN 2 + at clinics at three academic institutions over a 3-year period. Cytology, histology, patient age and time-to-excision were analyzed to determine factors influencing rates of regression. Of 356 women undergoing excision for CIN 2 + on colposcopic biopsy, 91 (25.3%) of final pathology diagnoses displayed clinically significant regression. Age and time-to-excision were not associated with regression, but referral cytology and severity of initial biopsy histology were, with ASC-H (aOR 0.1, CI 0.03, 0.8) and CIN 3/AIS (aOR 0.4, CI 0.2, 0.7) being less likely to regress than less severe lesions. Disease severity by referral cytology or diagnostic biopsy, as opposed to age or length of time-to-excision, is likely the most relevant factor in determination of regression for cervical intraepithelial neoplasia in women undergoing excisional treatment for biopsy-confirmed CIN2 +.

Human Papillomavirus and Cervical Intra-Epithelial Neoplasia: Epidemiological and Cytological Study in Lubumbashi Women

The objective of this study is to show that the presence of koilocytosis on the cervical smear is the only possibility to detect Papillomavirus infection in cervical intra-epithelial neoplasia in women living in Lubumbashi. This is a cross-sectional analytical study on the data collected from the register of women who participated in the cervix lesion screening campaign organized in Lubumbashi in March 2012 by the Congolese League Against Cancer. A total of 545 women with cervical lesions have been selected. The following results were observed: the frequency of HPV infection is 35% in Lubumbashi women. The risk of developing intraepithelial neoplasia is 38.3 times higher in women infected with HPV compared to uninfected ones (OR = 38.3, 95% CI = 16.3-90.3). HPV is predominantly present in intraepithelial neoplasia (92.7%) and this regardless of their grade: 91.9% for low-grade neoplasia and 95% for high-grade neoplasia. HPV is found in both older women and older women, respectively in 45% of women aged less than 36 years and in 55% of women aged over 36 years old. This study shows that it is necessary to put in place adequate means for the detection of HPV in order to contribute to the fight against cervical cancer in Lubumbashi.

Incidence of cervical intraepithelial neoplasia in women infected with human immunodeficiency virus (HIV) with no evidence of disease at baseline: Results of a prospective cohort study with up to 6.4 years of follow-up from India.

We report the incidence of cervical intraepithelial neoplasia (CIN) among HIV-infected women who did not have any colposcopic or histopathological evidence of CIN at baseline. Of the 1,023 women without any CIN at baseline, 855 (83.6%) have been followed up to a maximum of 6.4 years contributing 2,875 person years of observation (PYO). Among these 855 women, 54 cases of any CIN were observed resulting in incidence rate of any CIN of 1.9 per 100 PYO. The median time for follow-up for women with any CIN was 3.0 (IQR 1.6-3.7) years. The cumulative incidence rate per 100 PYO of CIN 2 or worse lesion in women with HPV-18 infection at baseline was 13.3% (95% CI 5.1-26.8); in women with HPV-16 infection was 10.8% (95% CI 4.4-20.9); in women with HPV-31 infection was 4.2% (95% CI 0.9-11.7); and in women with other high-risk HPV infections was 5.4% (95% CI 2.6-9.7). HPV-18 infection at baseline contributed highest frequency of incident CIN 2 or worse lesions followed by HPV-16 infection; however, other high-risk HPV types were also responsible for substantial number of incident CIN. The elevated risk of CIN2+ disease in the study cohort was non-significant in women with CD4 count <200, possibly because of the small number of cases. Our results emphasize the need for regular cervical cancer screening of HIV-infected women and urgent implementation of cervical cancer screening services in HIV programs in India and other low and middle-income countries.

Interactions between serum folate and human papillomavirus with cervical intraepithelial neoplasia risk in a Chinese population-based study

Although folate deficiency has long been implicated in cancer development, uncertainties remain concerning its role in cervical cancer prevention. In particular, the interaction between human papillomavirus (HPV) and folate in the risk of cervical intraepithelial neoplasia (CIN) has been little studied. The goal of this study was to evaluate the dose-response association of serum folate with the risk of CIN, and the potential for HPV to modify the risk of CIN. We performed a cross-sectional analysis of screening data in 2304 women aged 19-65 y who participated in an ongoing cohort of 40,000 women in China. Both categoric and spline analyses were used to evaluate the dose-response relation between serum folate and CIN risk. After adjusting for potential confounders, a statistically significant inverse association between serum folate concentration and at least grade 2 CIN (CIN2+) risk was observed (1st quartile compared with 4th quartile: OR=1.40; 95% CI: 1.09, 1.79; P-trend < 0.01); however, serum folate concentration was not associated with CIN1 risk. The risk patterns are similar when limited to only CIN2 and CIN3. An inverse linear relation between increased serum folate concentration and the risk of higher-grade CIN (CIN2, CIN3, and CIN2+) was also observed (for CIN2+: P-overall< 0.01, P-nonlinearity=0.96). The highest risk of CIN2+ was observed in women with high-risk HPV types, who also had the lowest serum folate concentrations (P-interaction<0.01). Our study indicates that serum folate is inversely associated with the risk of higher-grade CIN in Chinese women either with or without high-risk HPV infection. Thus, maintenance of normal serum folate levels may prove important for reducing the risk of CIN in women.

Human papillomavirus infection and associated factors for cervical intraepithelial neoplasia in women living with HIV in China: a cross-sectional study

ObjectiveWomen living with HIV (WLHIV) face disproportionately higher risks of acquiring human papillomavirus (HPV) compared with HIV negative counterparts. We aimed to investigate the prevalence of HPV in WLHIV in...

Associations of human gene EPB41L3 DNA methylation and cervical intraepithelial neoplasia in women living with HIV-1 in Africa.

To evaluate associations of DNA methylation of the human tumour suppressor gene EPB41L3 with high-grade cervical intraepithelial neoplasia (CIN2+) and HIV-related factors among women living with HIV-1 (WLHIV) in Burkina Faso and South Africa. Case-control study of WLHIV aged 25-50 with histology-determined CIN2+ (cases, N = 152) and ≤CIN1 (controls, N = 210). EPB41L3 methylation was measured by pyrosequencing of bisulphite converted DNA from exfoliated cervical specimens at baseline and 16 months later. Median methylation levels were compared across CIN grades using the Mann-Whitney test and Cuzick test for trend. EPB41L3 methylation levels were dichotomized into 'high' and 'low' using the 66.7 percentile point of the distribution in the controls. Associations of EPB41L3 methylation with HIV-related factors were estimated by logistic regression. Among 94 WLHIV in Burkina Faso and 268 in South Africa, median methylation levels at baseline for EPB41L3 increased with increasing CIN grade in both countries (P-trend <0.001).'High' methylation was more frequent among women with a longer time since HIV diagnosis in Burkina Faso [>5 years vs. ≤5 years; adjusted odds ratio (aOR) = 4.15, 95% CI 1.09-15.83, adjusted for age, CD4 count, high-risk HPV and CIN status], with low CD4 count in both countries (CD4 ≤200 vs. ≥350 cells/μl: aOR = 7.14, 95% CI 1.44-35.37 in Burkina Faso; aOR = 2.55, 95% CI 1.07-6.07 in South Africa), and with prolonged ART use in South Africa (ART >2 years vs. ART-naïve: aOR = 2.40, 95% CI: 1.23-4.69). Methylation of EPB41L3 DNA is elevated among WLHIV with CIN2+ and independently associated with lower CD4 count and ART use.

Abstract 3267: Cervical microbiota and the urinary metabolome in patients with high-risk and low-risk HPV infections

Abstract Genital human papillomavirus (HPV) is the world's most commonly diagnosed sexually transmitted infection, and high-risk HPV types are strongly linked to cervical dysplasia and carcinoma. The microbiota of the human cervico-vaginal tract is the interface between the host and environment, and its constituents may act as determinants of susceptibility for HPV infection. There exists the potential for reliable diagnostic biomarkers for cervical cancer in the cervical microbiome as well as in urine, which would be an important biospecimen due to its abundance and non-invasive collection strategy. In this study, we performed comprehensive metabolomic analysis on urine samples from 65 women (54 HPV+, 38 of whom have cervical intraepithelial neoplasia (CIN), and 11 HPV-) and discuss the potential diagnostic implication and metabolic description of high-risk and low-risk HPV infected patients. The experimental procedure employed gas chromatography mass spectrometry (GC-MS) on the urine-derived products and HPV genotyping was determined by reverse hybridization with the HPV SPF10-LiPA25 kit. We further characterized resident cervical bacteria in these patients using Illumina sequencing of the V4 region of the 16S ribosomal RNA with a high-resolution bioinformatics methodology (Resphera Insight v2.2) for species-level taxonomic assignment. The hybridization assay detected 11 low-risk and 10 high-risk HPV types many of them co-occurring in the cervical samples. Lactobacillus iners OTUs were shared by all samples but were significantly more dominant in women with low-risk HPV strains (p-value=0.05), while G. vaginalis, S. sanguinegens and L. jensenii were associated with high-risk strains. CIN1 and CIN3 dysplasic biopsies, detected significant enrichments of Gardnerella vaginalis, L.crispatus and Prevotella amnii (p-values &amp;lt;0.05). Preliminary GC-MS analysis identified elevated levels of palmitic (C16:0) and stearic fatty acids (C18:0) as well as lactic acid, abundant in the HPV+ samples while 5-oxo-proline and Neu5Ac (N-Acetylneuraminic acid) were abundant in the HPV- samples. Our preliminary data identifies possible microbial and metabolic biomarkers associated with oncogenic HPV and cervical intraepithelial neoplasia in women living in Puerto Rico. Citation Format: Gilmary Ortiz, Natalyia Chorna, Josefina Romaguera-Agrait, Magaly Martinez-Ferrer, Maria Sanchez, Ana P. Ortiz, Rafael Guerrero-Preston, James R. White, Filipa Godoy-Vitorino. Cervical microbiota and the urinary metabolome in patients with high-risk and low-risk HPV infections [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3267.

Effect of High-Risk Human Papillomavirus but Normal Cytology at Test of Cure on Achieving Colposcopy Standards.

In United Kingdom., test of cure after treatment of any grade of cervical intraepithelial neoplasia (CIN) incorporates high-risk human papillomavirus (Hr-HPV) test and cytology at 6-month follow-up. The aims of the study were to determine the rate of recurrent CIN in women who are Hr-HPV positive and cytology negative and to explore possible associated risk factors. A retrospective observational cohort study was performed in women treated for any grade CIN between 2010 and 2015 from a regional population, who were Hr-HPV positive and cytology negative at first follow-up. A total of 2729 women were identified as treated for any grade CIN, and 213 (7.8%) were re-referred to colposcopy having Hr-HPV-positive test and negative cytology at test of cure. Their mean age was 31.56 years (range = 19-62 years). The mean time of follow-up per woman was 30.50 months (range = 2-63 months). At colposcopy, 171 (80.3%) had colposcopy examination only and 42 women (19.7%) had a biopsy. Twenty-four cases (11.3%) of CIN were identified of which 4 (1.9%) were CIN 2/3. Eleven women (5.2%) in total had a repeat treatment. Five women (2.3%) had biopsy-proven CIN 2/3 within 12-months after treatment. No cases of CIN 3+ after negative colposcopy were identified during the follow-up period. The incorporation of Hr-HPV testing yielded a very small number of women with residual CIN within 12 months of treatment. Our results suggest that women who are Hr-HPV positive and cytology negative after treatment of CIN with normal and adequate colposcopy could be discharged to routine recall if confirmed by larger national data.