LSIL Group Research Articles

Statistically Significant Associations Between HPV33, HPV35, and HPV56 With Anal HSIL in a Population of MSMLWH.

The aim of the study is to determine the prevalence of high-risk human papillomavirus (hrHPV) genotypes in men who have sex with other men and are living with HIV and the factors associated with anal high-grade squamous intraepithelial lesions (HSIL). Anal swabs were collected for hrHPV genotyping from a cross-sectional group (N = 163) of eligible men who have sex with other men and are living with HIV attending a high-resolution anoscopy clinic. Persistent hrHPV infections were studied in a longitudinal subset (n = 37). Association of anal HSIL with specific hrHPV genotype(s) and with HIV-1 suppression was assessed. Pearson's χ2 test with continuity correction or Fisher's exact test was used to determine statistical significance (alpha = 0.05). Overall prevalence of hrHPV anal infections was 93.3% (152/163). Higher numbers of hrHPV genotypes were detected per sample in the HSIL group compared with less than or Low-grade squamous intraepithelial lesion (≤LSIL) group (p < .001). Proportion of participants infected with HPV33 was higher in the HSIL group (66.7%) than in ≤LSIL group (33.3%, p < .001), as was HPV35 (61.1% vs. 38.9%, p = .001) and HPV56 (56.7% vs. 43.3%, p = .022). HPV33 persistence was highly associated with HSIL (100%; 8/8) compared with ≤LSIL (0%; 0/8) (p < .001). Proportion of HIV-1 suppression (<200 cp/mL) was significantly lower among the HSIL group (80%; 48/60) compared with ≤LSIL group (95.1%; 97/102) (p = .006). Statistically significant associations existed between anal HSIL and HPV33, HPV35, and HPV56 infections, with HPV33 persistence, and with the lack of HIV-1 suppression. These findings emphasize the critical need for genotyping assays that differentiate more than just HPV16, HPV18 and a pool of "other" hrHPV genotypes and that have an intended use with anal specimens. Globally, this highest-risk population would benefit from the 9-valent vaccine to prevent infections and reduce anal cancer risk.

Clinical and epidemiological features of high-risk human papillomavirus infection in patients with cervical intraepithelial lesions

ObjectiveIn this study, we analyzed the clinical and epidemiological features of high-risk human papillomavirus (HR-HPV) infection in patients with cervical intraepithelial lesions.MethodsRetrospective analysis was performed on the clinical data of 240 cases of histologically confirmed cervical squamous intraepithelial lesions to determine any correlation between HPV infection characteristics, age distribution, and cervical epithelial lesions.ResultsPatients between the ages of 31 and 40 with cervical intraepithelial lesions were more likely to have high-grade squamous intraepithelial lesions (HSIL; 40.7%) than low-grade squamous intraepithelial lesions (LSIL; 31.3%) (P < 0.05). In patients with HSIL, HR-HPV16, HR-HPV33, and HR-HPV52 were the most common types of HPV infection, while in patients with LSIL, HR-HPV16, HR-HPV52, and HR-HPV58 were the most common types of HPV infection. The highest percentage of single infections occurred in the HSIL group (69.6%), followed by the LSIL group (68.8%). HSIL was present in a significant number of patients (28.6%) aged 30 years and above who tested positive for 12 HPV types but negative for TCT.ConclusionThe prevalence of HSIL is greatest in younger patients. Patients with cervical epithelial lesions typically have a single infection of a high-risk HPV genotype—HR-HPV16, HR-HPV33, HR-HPV52, or HR-HPV58. Patients aged 30 years and above who test positive for one of 12 types of HPV but negative for TCT are at increased risk for developing HSIL. In order to detect cervical lesions early and begin treatment without delay, colposcopy should be performed regardless of whether or not a high-risk HPV infection is present.

The relationship of immunohistochemical SOX-2 staining with histopathological diagnosis in patients with abnormal colposcopic findings.

This study aimed to analyze immunohistochemical staining and pathological data in cervical intraepithelial neoplasia (CIN) and squamous cell cervical carcinoma (SCC) with abnormal colposcopic findings. A histopathological evaluation of 45 low-grade squamous lesions (LSILs), 177 high-grade squamous lesions (HSILs) and 16 SCC biopsy materials from existing slides was obtained from blocks obtained from the archive. In addition, SOX-2 immunohistochemical staining was evaluated. The mean age of the HSIL group was 43.20 ± 8.97years, younger than the mean age of the LSIL group of 51.62 ± 9.64years (p = 0.000). There was no difference between the groups regarding the method of biopsy (p > 0.05). Endocervical gland involvement was not observed in the LSIL group, but was observed in 66 (37.3%) biopsy materials in the HSIL group (p = 0.000). There was a difference between the groups in terms of the level of CIN at the surgical margin (p = 0.000). Ki-67, SOX-2 staining percentage and p16INK4a positivity were higher in the HSIL group than in the LSIL group (respectively, 67.57 ± 19.10 vs. 14.62 ± 7.11, p = 0.000; 27.72 ± 31.56 vs. 10.09 ± 15.38, p = 0.003; 66 (82.5%) vs. 8 (44.4%), p = 0.001). While there was no difference in SOX-2 intensity between the HSIL and LSIL groups (p > 0.05), it was statistically significantly higher in the SCC group (p = 0.000), as was the percentage of SOX-2 (p = 0.000). We have shown that p16INK4a and SOX-2 staining is useful, in addition to Ki-67 immunostaining, which is widely used for SCC, which is one of the preventable cancer types. In addition, SOX-2 may provide a glimmer of hope in the development of SCC treatment modalities, especially since it is aggressively elevated in SCC rather than CIN lesions.

Association of MicroRNA-10b Expression and P16 with Pathological Features in Various Stages of Cervical Precancerous Lesions.

Cervical cancer is the fourth most prevalent cancer for females with 14,100 new cases each year globally. Efficient screening and intervention at the precancerous stage is the key point to the prevention and treatment of cervical cancer. However, no widely recognized biomarkers have been discovered yet. We investigated the expression of miR-10b in cervical cells and its correlation with clinicopathological features in different pathological grades of cervical precancerous lesions. The expression of miR-10b in cervical cytology samples from 20 cases of LSIL, 22 cases of HSIL, 18 cases of early-stage cervical cancer, and 20 cases of cervicitis controls were assessed using qPCR. From the same cervical cytology samples, the human papillomavirus (HPV) load was assessed using semi-PCR and the lesion size, and gland involvement levels from the same subjects were assessed during the cervical examination. The correlation between miR-10b expression and different pathological grades of cervical lesions was analyzed. We also calculated the correlation between HPV load, lesion size, gland involvement, P16 expression, and different pathological grades. The expression of miR-10b exhibited a step-decreasing manner from cervicitis control (4.23(4.00,4.71)) to LSIL (2.67(2.52,2.90)), HSIL (1.49(1.30,1.80)) and cervical cancer group (0.65(0.55,0.80)). There is a significant difference (P<0.001) between cervicitis and HSIL, cervicitis and cervical cancer, ISIL and HSIL, as well as ISIL and cervical cancer but not between the cervicitis group and the LSIL group. In addition, more severe pathological grades were correlated with a bigger rate of gland involvement (P＜0.001). We also found that different pathological grades were correlated with the intensity of P16 expression (P=0.001), and the intensity of P16 expression is positively correlated with different pathological grades (P<0.05). Repressed expression of miR-10b is related to the progression of cervical precancerous lesions. Increased gland involvement rate and increased intensity of P16 expression are risk factors for developing cervical cancers. Our result showed that miR-10b may be a potential biomarker for the screening and ranking of cervical precancerous lesions.

Comparison of Ki67 index and P16 expression in different grades of cervical squamous intraepithelial lesions.

the assessment of P16 expression and Ki-67 proliferative index is now proposed as an adjunct test for the diagnosis of high-risk precursor lesions for cervical cancer. The aim of the present study was to elucidate the quality expression of P16 and quantification Ki-67 index in different types of cervical intraepithelial neoplasia and also to determine the cutoff for Ki67 index to predict the severity of CIN lesions. This cross-sectional study was conducted on patients with colposcopic indication. Selected samples with different CIN grades were examined for P16 and Ki-67 index by immunohistochemical (IHC) methods. All LSIL (CIN I) cases were negative for P16, while in 58.7% of HSIL cases (CIN 2/3), P16 was positive. The mean Ki67 index in the present study was 3.13 ± 2.65 in the upper two/third of the squamous epithelium in the LSIL group and 19.04 ±36.40 in the HSIL group, which was statistically significant. Also, the mean Ki67 index in full thickness squamous epithelium in HSIL group was significantly higher than LSIL. The sensitivity of P16 and Ki67 index in our study was 58.73%, 66.67% and the specificity was 100% and 100%, respectively. Assessment of P16 expression and Ki67 index can be used to distinguish low grade (CIN1) intraepithelial lesion from high grade (CIN2/3) intraepithelial or precancerous lesions.

Analysis of Distributions of HPV Infection in Females with Cervical Lesions in the Western District of Beijing Chaoyang Hospital.

Objective To analyze the distribution of human papilloma virus (HPV) infection in women with cervical lesions of different grades and analyze the relationship of high-risk HPV and cervical lesions in order to facilitate targeted prevention. Methods The infection status of HPV subtype was statistically analyzed in patients who underwent colposcopy examination from April 2017 to June 2019. Results The infection rate of HPV was 81.4% in chronic cervicitis, 82.9% in 1ow-grade squamous intraepithelial lesion (LSIL), 63.7% in HSIL (high-grade squamous intraepithelial lesion), and 50% in cervical squamous cell carcinoma (CSCC). Among the 16 high-risk HPV types, the top six HPV types with the comprehensive infection rates were HPV16 > HPV52 > HPV58 > HPV18 > HPV51 > HPV53 in turn, and the infection rates were 23.3%, 14.8%, 13.3%, 9.8%, 9.2%, and 8.8%, respectively. The infection rates of HPV16 in chronic cervicitis group, LSIL group, and HSIL group were significantly different. There was no significant difference in the injection rates of HPV52, HPV58, and HPV18 among the three groups. HPV infection rates were highest in the 31–40 years old group, followed by the 41–50 years old group. Conclusion The distribution of different types of HPV varies in different tissue types, which can be used to develop relevant vaccines to achieve better prevention and treatment of cervical cancer.

Preliminary Study on the Expression of Testin, p16 and Ki-67 in the Cervical Intraepithelial Neoplasia.

Cervical cancer is one of the most common malignant cancers in women worldwide. The 5-year survival rate is 65%; nevertheless, it depends on race, age, and clinical stage. In the oncogenesis of cervical cancer, persistent HPV infection plays a pivotal role. It disrupts the expression of key proteins as Ki-67, p16, involved in regulating the cell cycle. This study aimed to identify the potential role of testin in the diagnosis of cervical precancerous lesions (CIN). The study was performed on selected archival paraffin-embedded specimens of CIN1 (31), CIN2 (75), and CIN3 (123). Moderate positive correlation was observed between testin and Ki-67 as well as testin and p16 expression in all dysplastic lesions (r = 0.4209, r = 0.5681; p < 0.0001 for both). Statistical analysis showed stronger expression of the testin in dysplastic lesions vs. control group (p < 0.0001); moreover, expression was significantly higher in HSIL than LSIL group (p < 0.0024). In addition, a significantly stronger expression of testin was observed in CIN3 vs. CIN1 and CIN3 vs. CIN2. In our study, expression of Ki-67, p16, and testin increased gradually as the lesion progressed from LSIL to HSIL. The three markers complemented each other effectively, which may improve test sensitivity and specificity when used jointly.

MicroRNA Levels in Cervical Cancer Samples and Relationship with Lesion Grade and HPV Infection.

miR-21, miR-214 and miR-let-7a are three validated and well-known miRNAs. miR-21 is described as an "oncomir" while miR-214 and miR-let-7a are described mainly as tumor suppressors. The role of these miRNAs remains unclear in cervical cancer, an important malignancy among women worldwide and responsible for many deaths every year. The objective of this study is to describe the expression profile of miR-21, miR-214 and miR-let-7a in plasma and in cervical scraping from a control group and patients with different grades of cervical lesions and invasive cervical cancer and correlate with HPV infection groups. Plasma and cervical scraping were submitted to DNA and RNA extraction. HPV detection and typing were performed by conventional PCR followed by PAGE to amplicons interpretation. The miRNA relative expression in plasma and cervical scraping samples was performed by real time PCR using specific TaqMan probes. miR-21 (p=0.0277) and miR-214 (p=0.0151) were up-regulated in cervical scraping samples of invasive cervical cancer (ICC) group. However, miR-214 was also up-regulated in the LSIL group (p=0.0062). Both miRNAs were not related to HPV infection. However, miR-let-7a was higher in HPV positive plasma samples (p=0.0433) than in HPV negative plasma samples and the correlation analysis confirmed the association between the levels of this miRNA with the presence of HPV (p=0.0407; r=0.3029), but not with lesion grade (p>0.05). Our results suggest that miR-21 is related to cervical cancer progression and miR-214 appears to have an ambiguous role in cervical lesions. miR-let-7a may be upregulated at a systemic level in patients with HPV infection.

The safety and efficacy of a novel method for treatment of HSIL.

To investigate the efficacy and safety of Nr-CWS on treatment of cervical HSIL. In this observational study, 16 patients were treated with Nr-CWS 1 time every 2days for 6 times as one-course group (OC group), the other 184 patients were treated with Nr-CWS 1 time every 2days for 12 times between 2 menstruations as two-course group (TC group). The medical information including age, HPV assay, vaginal-cervical cytology, and the pathological result of biopsy before and after treatment was collected. All patients were followed up at least twice after treatment. The LEEP was performed once the patients with persistent HR-HPV infection and/or abnormal TCT after the second follow-up. The cytology remission rate of cervical HSIL in OC and TC group was 100.0% and 87.8%, respectively, which were significant higher than the control (25.0%) with the P value of 2.00 × 10-3 and 2.06 × 10-4. Furthermore, HPV clearance rate was 87.5% and 70.2% in OC and TC group, respectively, which were significant higher than control (32.4%) with the P value of 2.74 × 10-4 and 2.18 × 10-5, respectively. Moreover, the more severe of cytology, the worse effect of HPV clearance for the HPV remission was 75.4%, 68.3%, 67.4%, 65.6% and 64.3% in the negative, LSIL, ASC-US, ASC-H, and HSIL group. 12 patients underwent LEEP after Nr-CWS treatment, 9 (75%) had persistent HSIL and 44.4% cases were found HSIL lesion in the cervical canal. There was no serious adverse reaction observed during treatment and follow-up, four patients were pregnant after treatment and no adverse pregnancy outcomes were observed. Nr-CWS is an effective and safe drug for treatment of cervical HSIL for Chinese women, especially for cases without lesions in cervical canal.

Human papillomavirus infection and cervical intraepithelial neoplasia progression are associated with increased vaginal microbiome diversity in a Chinese cohort

BackgroundIn this study, the association between human papillomavirus (HPV) infection and related cervical intraepithelial neoplasia (CIN) or cervical cancer and vaginal microbiome was evaluated in Chinese cohorts.MethodsThe vaginal bacterial composition of five groups, HPV-infected women without CINs (HPV, n = 78), women with low-grade squamous intraepithelial lesions (LSIL, n = 51), women with high-grade squamous intraepithelial lesions (HSIL, n = 23), women with invasive cervical cancer (Cancer, n = 9) and healthy women without HPV infection (Normal, n = 68), was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V3–4) using Illumina MiSeq.ResultsHPV infection increased vaginal bacterial richness and diversity regardless of the status of CINs. The vaginal bacterial richness and diversity were further augmented in women with cervical cancer. Lactobacillus was the most abundant genus in all groups. HPV infection had a negative influence on the abundances of Lactobacillus, Gardnerella and Atopobium. Accordingly, HPV infection increased the relative abundance of Prevotella, Bacillus, Anaerococcus, Sneathia, Megasphaera, Streptococcus and Anaerococcus. The increased proportions of Bacillus, Anaerococcus and the reduced abundance of Gradnerella vaginalis were probably related with the progression of CINs severity. HPV infection without CINs or cancerous lesions was strongly associated with Megasphaera. The most abundant bacterium in the LSIL group was Prevotella amnii. However, Prevotella timonensis, Shuttleworthia and Streptococcaceae at the family level were three taxa related to HSIL. Furthermore, more taxa were associated with the Cancer group including Bacillus, Sneathia, Acidovorax, Oceanobacillus profundus, Fusobacterium, Veillonellaceae at the family level, Anaerococcus and Porphyromonas uenonis. Samples in the Normal group were mostly assigned to CST III. HPV infection converted the vaginal bacterial community structure from CST III to CST IV. Furthermore, the proportions of CST IV were gradually augmented with the progression of the severity of CINs.ConclusionsThis work interpreted the differential vaginal bacteria under HPV infection and various precancerous or cancerous lesions in a Chinese cohort. We distinguished the specific microbes and the vaginal bacterial structure that were related with the progression of CINs severity in Chinese women.

Application of CircEIF4G2 in Screening of Cervical Lesions.

The aim was to investigate the expression of circulating RNA EIF4G2 (CircEIF4G2) in cervical cancer and its correlation with clinicopathological features. Cervical tissue and peripheral blood serum samples were collected from 148 patients with cervical lesions, including 30 patients with low-grade squamous intraepithelial lesions (LSIL group), 35 patients with high squamous intraepithelial lesion (HSIL group), 28 patients with atypical squamous cells (ASC group), and 55 patients with cervical cancer (CC group). At the same time, cervical biopsy specimens and peripheral blood serum were collected from 40 healthy women (Normal group). RT-PCR was used to detect the expression of CircEIF4G2 in cervical tissues and peripheral blood of each group. Electron microscopy was used to observe the distribution of exosomes CircEIF4G2 in cervical tissues. Meanwhile, the correlation between the expression level of CircEIF4G2 and clinical pathological data of patients was analyzed. In vitro, HeLa cells and primary cervical epithelial cells were cultured for 24 hours. Then, the expression levels of CircEIF4G2 in the two kinds of cells were detected by RT-PCR in medium. Furthermore, primary cervical epithelial cells were co-cultured with HeLa cells to observe the effect of exosome CircEIF4G2 on primary cervical epithelial cells. The expression of CircEIF4G2 in the cervical tissue and serum of the normal group was significantly lower than that in the CC group (p < 0.05), but there was no significant difference between the LSIL group and the HSIL group in the cervical tissue and serum (p < 0.05). The distribution and expression of exosomes CircEIF4G2 in each group were consistent with RT-PCR results under an electron microscope. The results of experiments in vitro showed that the expression level of CircEIF4G2 in HeLa cells was significantly higher than that in primary cervical epithelial cells (p < 0.05). The medium in which Hela cells were cultured for 24 hours was added to the culture medium of primary cervical epithelial cells. The process of exosomes CircEIF4G2 entering primary cervical cancer cells was observed by electron microscopy. The increased expression of CircEIF4G2 in tissues and serum of cervical lesions may be caused by the secretion of exosomes containing CircEIF4G2 by cervical cancer cells. Therefore, CircEIF4G2 can be used as a marker for the diagnosis of cervical lesions.

Reproductive and Lifestyle Characteristics of Kenyan Women Presenting With Precancerous Cervical Lesions: A Hospital-Based Case–Control Study

Background: Cervical cancer is a leading cause of cancer in women, accounting for 68% of cancer-related deaths among women in developing countries. Several reproductive, lifestyle and demographic risk factors are associated with increased risk for cervical cancer. This study examined the association of risk factors with precancerous cervical lesion grade in women attending Nakuru County Referral Hospital. Methods: This hospital-based, case-control study was conducted among women aged 20 to 70 years from January to December, 2017. A total of 142 women were recruited into the study and stratified based on precancerous cervical lesion grades based on the Bethesda System as: atypical glandular cells or adenocarcinoma in situ (AGC/AIS, n=8), high-grade squamous intraepithelial lesions (HSIL, n=59), low-grade squamous intraepithelial lesions (LSIL, n=35), and controls (n=40). Structured questionnaires were used to collect information on demographic, reproductive health, and lifestyle characteristics; anthropometric assessments were conducted. Endocervical swabs and scrapings were obtained from the study participants and used for human papillomavirus (HPV)-16/18, and Pap smear screening. Results: Age differed significantly among the study groups, with age rising with higher grade of precancerous lesion. Higher rates of HPV 16/18 infection was associated with presenting with AGC/AIS (n=8, 100.0%), HSIL (n=47, 79.7%), and (n= 29, 82.9%), compared to controls (n=4, 10.0%; P<.001). History of concomitant lower abdominal pain, vaginal bleeding and discharge was associated with higher risk of precancerous lesion in the HSIL group (odds ratio [OR] 8.9; 95% confidence interval [CI], 2.6 to 30.6) and the LSIL group (OR 5.8; 95% CI, 1.8 to 18.8). Bust circumference <99 cm was associated with higher risk of having AGC/AIS (OR 17.4; 95% CI, 1.1 to 276.0), HSIL (OR 5.9; 95% CI, 2.0 to 17.1), and LSIL (OR 2.7; 95% CI, 0.9 to 7.8). Waist circumference <86 cm was associated with higher risk of HSIL (OR, 5.4; 95% CI, 1.9 to 15.4) and LSIL (OR 2.9; 95% CI, 0.9 to 8.2). Having a healthy diet was associated with higher odds of LSIL (OR, 4.2; 95% CI, 1.4 to 12.9), but was not associated with HSIL or AGC/AIS. Conclusion: This study suggests that high-risk HPV 16/18 infection, chronic lower abdominal pain with vaginal bleeding, and decreased upper and lower trunk body mass, are associated with higher risk of precancerous cervical lesions. Integrating targeted cervical cancer screening in routine reproductive health-care services may reduce the risk of developing cervical cancer.

Expression and clinical significance of galectin-9 in different cervical lesions and different types of human papillomavirus infection

Objective To analyze the expression differences and clinical significance of galectin 9(Gal-9) in different cervical lesions and human papillomavirus(HPV) type infection. Methods From May 2016 to April 2018, 42 cases of cervical cancer(CC group), 45 cases of high level cervical intraepithelial neoplasia (HSIL group), 45 cases of lower cervical intraepithelial neoplasia (LSIL group) in Yangzhou Maternal and Child Health-Care Hospital were selected, and 45 cases of normal outpatient medical examination in our hospital were selected as the control group(NC group). Enzyme-linked immunosorbent assay(ELISA) method was used to detect the serum level of Gal-9.The gene amplification technique and the principle of diversion hybridization were used to detect the 37 types of HPV. Results Of women with cervical lesions, 50 cases(28.3%) were 50 years or more, the CC group had 32 cases (76.2%), HSIL group had 10 cases (22.2%), LSIL group had 8 cases (17.8%), the age of CC group compared with HSIL group and LSIL group had significant differences(t=7.959, 10.440, all P<0.01). The serum level of Gal-9 in CC group [(22.27±1.72)ng/L], HSIL group [(15.43±2.14)ng/L], LSIL group [(15.24±1.89)ng/L] was significantly higher than that in NC group [(12.08±2.13)ng/L](t=16.360, 18.100, 24.440, all P<0.05). The HPV infection rate in patients with cervical lesions reached 84.84%(112/132), the positive rate of HPV16 in CC group was 83.3%(35/42), HSIL group was dominated by HPV16(28.8%), HPV33(20.0%), HPV52(17.7%) and HPV58(13.3%), LSIL group was dominated by HPV52(26.7%), HPV58(24.4%), HPV16(20.0%) and HPV18(8.9%). There was no statistically significant difference in the levels of Gal-9 of HPV16, HPV58, HPV52 and HPV33 patients, indicated that there was no statistically significant correlation between Gal-9 level and the type of HPV infection. Conclusion Early intervention in patients with high HPV infection and Gal-9 levels can help reduce the incidence of cervical cancer. Key words: Galectins; Uterine cervical diseases; Uterine cervical neoplasms; Carcinoma, squamous cell; Cervical intraepithelial neoplasia; Human papillomavirus; Genotype; Gene expression

Atipias de células escamosas de significado incierto (ASCUS) y lesión escamosa intraepitelial de bajo grado (LSIL). Control citológico evolutivo a 3 meses. Resultados

ObjectiveProspective study of 4 years (2015-2018) of the ASCUS and LSIL cases in the vaginocervical cytology, and your evolutive cytological control in 3 months. DesignStudy of: age, parity, nulligravides, menopausal, contraceptive methods, sexuality and sexual dysfunctions, pathologic antecedents, cytology and HPV (human papillomavirus) analysis, comparing the evolution in both groups. ResultsThe series are 146 cases of ASCUS and 82 cases of LSIL.In ASCUS, there were significant differences in age (P<.02), parity (P<.001), and abortions (P<.02). In LSIL, there were significant differences in nulligravides (P<.001).There were significant differences (P<.02) in condom use in LSIL. In both groups more of 50% of the cases dońt use any contraceptive method There were no significant differences in sexuality nor in sexual dysfunctions, neither in antecedents.ASCUS was associated with infections in 15,05%. LSIL was associated with infections in 9,74%, without differences.There were significant differences in negative HPV (P<.001) in ASCUS, 43,15% versus 20,73% in LSIL. There were significant differences in High Risk other viruses positive (P<.001) in LSIL.In the cytologic control at 3 monts, there were significant differences in ASCUS+BV (bacterial vaginosis) (P<.02) in LSIL. Also in LSIL group there were more LSIL in the cytologic control at 3 months, 26,82% (P<.01).In the follow-up at 1 year, there were no significant differences. The negative cytology was in 64,86% and 47,82%, respectively. ConclusionThe reiterative cytology in 3 months are value for detecting the associated infections, and treated; to run over and advance the cytologic normality.

Reproductive and Lifestyle Characteristics of Kenyan Women Presenting With Precancerous Cervical Lesions: A Hospital-Based Case-Control Study.

Background:Cervical cancer is a leading cause of cancer in women, accounting for 68% of cancer-related deaths among women in developing countries. Several reproductive, lifestyle and demographic risk factors are associated with increased risk for cervical cancer. This study examined the association of risk factors with precancerous cervical lesion grade in women attending Nakuru County Referral Hospital.Methods:This hospital-based, case-control study was conducted among women aged 20 to 70 years from January to December, 2017. A total of 142 women were recruited into the study and stratified based on precancerous cervical lesion grades based on the Bethesda System as: atypical glandular cells or adenocarcinoma in situ (AGC/AIS, n=8), high-grade squamous intraepithelial lesions (HSIL, n=59), low-grade squamous intraepithelial lesions (LSIL, n=35), and controls (n=40). Structured questionnaires were used to collect information on demographic, reproductive health, and lifestyle characteristics; anthropo-metric assessments were conducted. Endocervical swabs and scrapings were obtained from the study participants and used for human papillomavirus (HPV)-16/18, and Pap smear screening.Results:Age differed significantly among the study groups, with age rising with higher grade of precancerous lesion. Higher rates of HPV 16/18 infection was associated with presenting with AGC/AIS (n=8, 100.0%), HSIL (n=47, 79.7%), and (n= 29, 82.9%), compared to controls (n=4, 10.0%; P<.001). History of concomitant lower abdominal pain, vaginal bleeding and discharge was associated with higher risk of precancerous lesion in the HSIL group (odds ratio [OR] 8.9; 95% confidence interval [CI], 2.6 to 30.6) and the LSIL group (OR 5.8; 95% CI, 1.8 to 18.8). Bust circumference <99 cm was associated with higher risk of having AGC/AIS (OR 17.4; 95% CI, 1.1 to 276.0), HSIL (OR 5.9; 95% CI, 2.0 to 17.1), and LSIL (OR 2.7; 95% CI, 0.9 to 7.8). Waist circumference <86 cm was associated with higher risk of HSIL (OR, 5.4; 95% CI, 1.9 to 15.4) and LSIL (OR 2.9; 95% CI, 0.9 to 8.2). Having a healthy diet was associated with higher odds of LSIL (OR, 4.2; 95% CI, 1.4 to 12.9), but was not associated with HSIL or AGC/AIS.Conclusion:This study suggests that high-risk HPV 16/18 infection, chronic lower abdominal pain with vaginal bleeding, and decreased upper and lower trunk body mass, are associated with higher risk of precancerous cervical lesions. Integrating targeted cervical cancer screening in routine reproductive health-care services may reduce the risk of developing cervical cancer.

Performance of P16/Ki67 dual staining in triaging hr-HPV-positive population during cervical Cancer screening in the younger women

BackgroundCervical cancer is the most common malignancy from the female reproductive tract, and usually develops from low-grade or high-grade squamous intraepithelial lesions (LSIL or HSIL). Detecting the precancerous lesion during the LSIL-HSIL-invasive cancer sequelae can effectively interrupt the oncogenesis and decrease the incidence of invasive carcinoma. The aim of this study is to evaluate the performance of P16/Ki67 dual staining in triaging hr-HPV-positive population. MethodsConventional gynecological examination, cervical cytology and hr-HPV testing were given to all patients. Specimens were collected for cytology examination and HPV genotyping. According to cytology results, patients were divided into cervical cancer group, HSIL group, LSIL group and benign lesion group. Sensitivity and specificity of the dual staining method in each histopathologic group was obtained and compared. ResultsAmong the108 patients participated in the study, 65 were diagnosed as normal, 15 as LSIL, 20 as HSIL and 8 as CC, by histopathologic examination. Dual staining of p16/Ki67 on cytology specimen provided a positive predictive value of 86% and the negative predictive value of 96%. The sensitivity approached 96.43% when combining ThinPrep cytological test (TCT) with the dual staining, with a specificity of 60% in detecting HSIL. Joint detection of TCT and p16/Ki67 dual staining displayed the highest specificity among all the attempted combinations of detection methods. ConclusionsThis study demonstrated that p16/Ki-67 dual staining represents an effective method for cervical cancer screening. Application of this method could lead to a reduction of unnecessary colposcopy referrals and misdiagnosis.

Role of p16/Ki-67 Dual Immunostaining in Detection of Cervical Cancer Precursors.

Background:Pap-smears-based cytology and human papilloma virus testing have their own limitations in detecting cervical precancerous lesions, and still need further standardization. Co-expression of p16ink4a and Ki-67 can be used as additional biomarker.Aims:To study the role of liquid-based cytology and the dual immunostaining for p16/Ki-67 in predicting the presence of significant lesion in cases of mild cytological atypia.Materials and Methods:A prospective, cross-sectional study was performed in the Department of Pathology, in collaboration with Department of Obstetrics and Gynecology over 15 months including 545 patients. Immunocytochemistry followed by colposcopy-guided biopsy were performed in 52 cases with epithelial abnormalities.Results:Thirty-five cases (67%) were dual-stain positive among the cases with epithelial abnormalities. In the ASC-US and LSIL group, the sensitivity and specificity of the immunostaining in diagnosing CIN2+ lesions were 100 and 70% and 87.5 and 100%, respectively. p16/Ki-67 positivity also increased with cytological severity which in turn corresponded with histological findings: it reached from 33% in ASC-US to 100% in both HSIL and SCC categories.Conclusion:This dual immunostaining may potentially be a useful tool in the triage of the ASC-US and the LSIL group, considering the high sensitivity and specificity values.

Clinical significance of atypical squamous cells of undetermined significance after treatment for cervical intraepithelial grade 3 neoplasia: A retrospective single-center cohort study.

The aim of the present study was to evaluate the clinical significance of atypical squamous cells of undetermined significance (ASC-US) following cervical conization for cervical intraepithelial neoplasia (CIN) grade 3. This study was a retrospective cohort analysis. The medical records of women treated with conization for CIN 2-3 were reviewed and 142 patients with CIN 3 who had been diagnosed using the conization specimens were selected. The mean follow-up period after conization was 41.8 months. Cytological abnormalities after conization were observed in 19.0% of the patients and consisted of ASC-US (13.4%) and worse than low-grade squamous intraepithelial lesion (LSIL; 5.6%). Recurrence was defined as a diagnosis worse than CIN 2, and the recurrence rate was 29.6% among patients with abnormal cytology. The recurrence rate was 15.7% in the ASC-US group and 71.4% in the worse than LSIL group. There was no significant difference in the time of initial identification of abnormal cytology after treatment between the worse than LSIL and the ASC-US groups (P=0.054). However, the ASC-US group had a significantly better cumulative recurrence-free rate compared with the worse than LSIL group (P<0.05). Women with ASC-US following treatment for CIN appear to be at a relatively high risk. Regarding the risk stratification of women following treatment for CIN, if surveillance cytology shows ASC-US, immediate colposcopy is recommended, along with long-term follow-up.

HPV16 E6 polymorphism and physical state of viral genome in relation to the risk of cervical cancer in women from the south of Poland.

The aim of this study was to analyse the correlation between HPV16 E6 variants and the physical status of viral genome (integrated, mixed, episomal) among patients with cervical cancer (n=40) and low-grade squamous intraepithelial lesions - LSIL (n=40). The study was performed on 80 HPV16 positive samples. HPV16 E6 variants were identified using PCR and DNA sequencing. Nucleotide sequences of E6 were compared with the prototype sequence (EUR-350T). The physical state of HPV DNA was determined as the ratio of E2/E6 copy number per cell. Twelve different intratypic variants were identified as belonging to European (in 77 samples) and North-American 1 (in 3 samples) sublineages. The most prevalent non-synonymous variant was EUR-350G, which occurred with similar frequency in cervical cancer and LSIL. The frequencies of additional mutations in variants with EUR-350T or EUR-350G sequences differed significantly. For the first time, missense mutations G122A, C153T and G188A were discovered in EUR-350G variant. The integrated viral genome was predominant in women with cervical cancer. The EUR-350T prototype and EUR-350G without additional mutations variants were prevalent in cervical cancer samples with the HPV16 characterized by integrated DNA. In summary, European variants of HPV16 E6 dominated in both cancer and LSIL group. The presence of EUR-350G favoured the occurrence of additional nucleotide changes. We showed that nucleotide changes occur significantly more often in the mixed form of viral DNA and in LSIL group and that the variants without additional mutations may promote integration of HPV16 genome.

ALDH2 polymorphism for the risk of cervical carcinogenesis.

To investigate the clinical significance of ALDH2 genetic polymorphisms in cervical carcinogenesis. ALDH2 polymorphisms together with human papillomavirus (HPV) types were examined in a total of 195 cervical smear in exfoliated cervical cell samples using Real-Time polymerase chain reaction (PCR) System. The frequency for the AG+AA genotype was seven in the normal group (70.0 %), 16 in the LSIL group (57.1 %), and 27 in the HSIL group (90.0 %). A significant difference was found between the LSIL and HSIL groups (P = 0.0064). Patients with HSIL lesions frequently had high-risk HPV infections and concurrently belonged to the AG+AA group. ALDH2 genotype in cervical cell samples may be associated with more severe precancerous lesions of the cervix in a Japanese population.