Different Grades Of Cervical Intraepithelial Neoplasia Research Articles

Mueller matrix-based characterization of cervical tissue sections: a quantitative comparison of polar and differential decomposition methods.

Quantitative optical polarimetry has received considerable recent attention owing to its potential for being an efficient diagnosis and characterizing tool with potential applications in biomedical research and various other disciplines. In this regard, it is crucial to validate various Mueller matrix (MM) decomposition methods, which are utilized to extract and quantify the intrinsic individual polarization anisotropy properties of various complex optical media. To quantitatively compare the performance of both polar and differential MM decomposition methods for probing the structural and morphological changes in complex optical media through analyzing their intrinsic individual polarization parameters, which are extracted using the respective decomposition algorithms. We also intend to utilize the decomposition-derived anisotropy parameters to distinguish among the cervical tissues with different grades of cervical intraepithelial neoplasia (CIN) and to characterize the healing efficiency of an organic crystal. Polarization MM of the cervical tissues with different grades of CIN and the different stages of the self-healing crystal are recorded with a home-built MM imaging setup in the transmission detection geometry with a spatial resolution of . The measured MMs are then processed with both the polar and differential MM decomposition methods to extract the individual polarization parameters of the respective samples. The derived polarization parameters are further analyzed to validate and compare the performance of both the MM decomposition methods for probing and characterizing the structural changes in the respective investigated optical media through their decomposition-derived intrinsic individual polarization properties. Pronounced differences in the decomposed-derived polarization anisotropy parameters are observed for cervical tissue sections with different grades of CIN. While a significant increase in the depolarization parameter is obtained with the increment of CIN stages for both the polar [ for CIN grade one (CIN-I) and for CIN grade two (CIN-II))] and differential ( for CIN-I and for CIN-II) decomposition methods, a trend reversal is seen for the linear diattenuation parameter , indicating the structural distortion in the cervical morphology due to the CIN disease. More importantly, with the differential decomposition algorithm, the magnitude of the derived parameter decreases from 0.26 to 0.19 with the progression of CIN, which was not being probed by the polar decomposition method. Our results demonstrate that the differential decomposition of MM holds certain advantages over the polar decomposition method to characterize and probe the structural changes in the cervical tissues with different grades of CIN. Although the quantified individual polarization parameters obtained through both the MM decomposition methods can be used as useful metrics to characterize various optical media, in case of complex turbid media such as biological tissues, incorporation of the differential decomposition technique may yield more efficient information. Also, the study highlights the utilization of MM polarimetry with an appropriate decomposition technique as an efficient diagnostic and characterizing tool in the realm of biomedical clinical research, and various other disciplines.

Predict the Progression of Cervical Intraepithelial Neoplasia by a Novel Marker Folate Combine with FRα, p16 and Ki-67.

PurposeTo study the expression of serum folate and red blood cell (RBC) folate, folate receptor α (FRα), p16INK4a (p16), and Ki-67 at different levels of cervical intraepithelial neoplasia (CIN) and then analyze their role in the progression of CIN and their value as an early warning indicator of CIN progression.Patients and methodsWe randomly collected the data of patients at the Department of Gynecology in Guangxi Medical University Affiliated Cancer Hospital from January 2016 to December 2018: Normal controls (149 cases), CIN1 (150 cases), CIN2 (100 cases), and CIN3 (101 cases). [Ethical approval by Ethics Committee of the Second Hospital of Shanxi Medical University. (2013) No. (001–1)]. The expression of serum folate and RBC folate was detected by the chemiluminescence method, while the expression of FRα, p16, and Ki-67 was detected by Streptavidin-Perosidase (SP) immunohistochemistry.ResultsThere was no statistically significant difference in serum folate levels between different grades of CIN (P=0.784), but the RBC folate levels were statistically significant (P=0.015), and there was a negative correlation between RBC folate levels and CIN lesion grades (P<0.05). The FRα, p16, and Ki-67 levels in the CIN group were significantly different from those in the normal control group (P <0.01), and a positive correlation was found (P <0.01); FRα positivity (P=0.000), Ki-67 positivity (P=0.000), and low-level RBC folate (P=0.000) were independent risk factors for the progression of CIN; these indicators were combined to establish a random forest (RF) model in which the Ki-67+FRα model was used as the early warning model of CIN progression.ConclusionRBC folate, FRα, p16, and Ki-67 can be used as valuable clinical test indicators for predicting the progression of CIN; the combined detection model of Ki-67+FRα can be used as an early warning model for predicting the progression of CIN.

Expression of p63 in Cervical Intraepithelial Neoplasia (CIN) and Cervical Cancer

Background: Cervical cancer is a major public health problem worldwide. Persistent infection with High-Risk Human Papilloma Virus (HPV) has been the main cause of squamous intraepithelial neoplasia which in turn leads to invasive squamous cell carcinoma. p63 is necessary for the activation of HPV, epithelial proliferation and differentiation. It also regulates the expression of certain cell cycle regulators. It has been reported that, from CIN I to CIN III, p63 expression increases progressively from basal layer to surface. In squamous cell carcinoma, it is expressed throughout the entire thickness of the tumor. Thereby it plays a significant role in diagnosing cervical premalignant and malignant lesions.&#x0D; Objective: To evaluate the relationship of p63 expression with different grades of CIN &amp; invasive SCC.&#x0D; Method: Total 86 paraffin embedded tissue blocks of histopathologically diagnosed cases of CIN and cervical cancer were evaluated by immunohistochemical staining for p63 expression. The study was performed in Sir Salimullah Medical College, Dhaka (from March, 2018 to February, 2020). Statistical analyses were carried out by using SPSS version 22 for Windows. A descriptive analysis was performed for all data. Observations were indicated by frequencies and percentages. Statistical significance was set at “p” value &lt;0.05.&#x0D; Results: Present study showed progressive increase in p63 expression from CIN I to CIN III from basal layer to surface. In invasive squamous cell carcinoma, higher expression of p63 was noted throughout the entire thickness of the tumor. No expression was seen in cervical adenocarcinoma and small cell carcinoma. In adenosquamous carcinoma only the area showing squamous differentiation revealed positive p63 expression. Statistically significant association of p63 expression was found with parity of patients and among grades of CIN .&#x0D; Conclusion: The results of this current study revealed that, p63 has significant association among different grades of CIN. It is also a useful marker in confirming a poorly differentiated squamous cell carcinoma &amp; predicting the progression of a squamous neoplastic lesion from cervical intraepithelial neoplasia to invasive squamous cell carcinoma. Moreover, it is useful to differentiate invasive squamous cell carcinoma from cervical adenocarcinoma.&#x0D; Sir Salimullah Med Coll J 2021; 29(2): 141-146

Identificación de cofactores nutricionales asociados a neoplasia intraepitelial cervical en mujeres de San Luis Potosí

Cervical Cancer (CeCa) is a public health problem worldwide. The natural history of the disease goes through different degrees of cervical intraepithelial neoplasms that modulate its transformation, depending on various co-factors related to the eating habits of patients, overweight and obesity, the consumption of food supplements and the intake of light products. The objective of this article is to identify those nutritional co-factors associated with the development of cervical intraepithelial neoplasia (CIN) in women from the city of San Luis Potosí, through the study of cases (100) and controls (300) of patients diagnosed with different grades of CIN by colposcopy, in addition to this, a validated questionnaire was applied, descriptive and inferential statistics were carried out, as well as the calculation of Odds Ratio (OR). The results indicate that the nutritional co-factors identified with a statistical significance were the intake of light and green tea soft drinks, as they are linked to the appearance of cervical intraepithelial neoplasm.

Within-Host Variations of Human Papillomavirus Reveal APOBEC Signature Mutagenesis in the Viral Genome.

Persistent infection with oncogenic human papillomaviruses (HPVs) causes cervical cancer, accompanied by the accumulation of somatic mutations into the host genome. There are concomitant genetic changes in the HPV genome during viral infection; however, their relevance to cervical carcinogenesis is poorly understood. Here, we explored within-host genetic diversity of HPV by performing deep-sequencing analyses of viral whole-genome sequences in clinical specimens. The whole genomes of HPV types 16, 52, and 58 were amplified by type-specific PCR from total cellular DNA of cervical exfoliated cells collected from patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) and were deep sequenced. After constructing a reference viral genome sequence for each specimen, nucleotide positions showing changes with >0.5% frequencies compared to the reference sequence were determined for individual samples. In total, 1,052 positions of nucleotide variations were detected in HPV genomes from 151 samples (CIN1, n = 56; CIN2/3, n = 68; ICC, n = 27), with various numbers per sample. Overall, C-to-T and C-to-A substitutions were the dominant changes observed across all histological grades. While C-to-T transitions were predominantly detected in CIN1, their prevalence was decreased in CIN2/3 and fell below that of C-to-A transversions in ICC. Analysis of the trinucleotide context encompassing substituted bases revealed that TpCpN, a preferred target sequence for cellular APOBEC cytosine deaminases, was a primary site for C-to-T substitutions in the HPV genome. These results strongly imply that the APOBEC proteins are drivers of HPV genome mutation, particularly in CIN1 lesions.IMPORTANCE HPVs exhibit surprisingly high levels of genetic diversity, including a large repertoire of minor genomic variants in each viral genotype. Here, by conducting deep-sequencing analyses, we show for the first time a comprehensive snapshot of the within-host genetic diversity of high-risk HPVs during cervical carcinogenesis. Quasispecies harboring minor nucleotide variations in viral whole-genome sequences were extensively observed across different grades of CIN and cervical cancer. Among the within-host variations, C-to-T transitions, a characteristic change mediated by cellular APOBEC cytosine deaminases, were predominantly detected throughout the whole viral genome, most strikingly in low-grade CIN lesions. The results strongly suggest that within-host variations of the HPV genome are primarily generated through the interaction with host cell DNA-editing enzymes and that such within-host variability is an evolutionary source of the genetic diversity of HPVs.

Human papillomavirus infection among Bangladeshi women with cervical intraepithelial neoplasia and chronic cervicitis

Background and objectives: Cervical cancer is one of the leading causes of morbidity and mortality. Human papillomavirus (HPV) is known to be associated with cervical intraepithelial neoplasia (CIN) and cancer. The objective of the present study was to determine the rate of HPV infection among the Bangladeshi women with different grades of CIN and cancer.Methods: Women aged 20 to 55 years, diagnosed as a case of chronic cervicits, cervical intraepithelial neoplasia (CIN) or invasive cancer by Papanicolaou (Pap) smear and colposcopy directed biopsy were enrolled in the study. High and intermediate risk oncogenic HPV were detected in cervical samples by real time PCR (rt-PCR).Results: Seventy two women with chronic cervicitis and different grades of CIN were included in the study. Out of 72 cases, 28 (38.9%) and 44 (61.1%) had chronic cervicitis and CIN respectively. Overall, the HPV infection rate was 43.1% (95% CI= 32%-54%) among the study population. CIN cases had significantly high (p&lt;0.01) HPV infection (78.6%; 95% CI=60%-89%) compared to cases with chronic cervicitis (18.2%; 95% CI=11.1%-34.5%). Women between the age of 20-30 years had the highest positive rate (50.0%) followed by 31- 40 years age group (43.6%). All CIN grade 2 and 3 had HPV infection.Conclusion: The study showed that HPV was strongly associated with different grades of CIN. Specific HPV types should be determined to find out the most prevalent HPV types among the Bangladeshi women with CIN and cervical cancers.IMC J Med Sci 2016; 10(1): 29-32

The relationship between the cervical and anal HPV infection in women with cervical intraepithelial neoplasia

BackgroundMore than 90% of cases of anal cancers are caused by high-risk human papillomavirus (HR HPV) infection and a history of cervical intraepithelial neoplasia (CIN) is established as possible risk factor. ObjectivesTo demonstrate relationship between anal and cervical HPV infection in women with different grades of CIN and microinvasive cervical cancer. Study designA total of 272 women were enrolled in the study. The study group included 172 women who underwent conization for high-grade CIN or microinvasive cervical cancer. The control group consisted of 100 women with non-neoplastic gynecologic diseases or biopsy-confirmed CIN 1. All participants completed a questionnaire detailing their medical history and sexual risk factors and were subjected to anal and cervical HPV genotyping using Cobas and Lynear array HPV test. ResultsCervical, anal, and concurrent cervical and anal HPV infections were detected in 82.6%, 48.3% and 42.4% of women in the study group, and in 28.0%, 26.0% and 8.0% of women in the control group, respectively. The prevalence of the HR HPV genotypes was higher in the study group and significantly increased with the severity of cervical lesion. Concurrent infections of the cervix and anus occurred 5.3-fold more often in the study group than in the control group. Any contact with the anus was the only significant risk factor for development of concurrent HPV infection. ConclusionsConcurrent anal and cervical HR HPV infection was found in nearly half of women with CIN 2+. The dominant genotype found in both anatomical locations was HPV 16. Any frequency and any type of contact with the anus were shown as the most important risk factor for concurrent HPV infection.

Characterising the local immune responses in cervical intraepithelial neoplasia: a cross‐sectional and longitudinal analysis

Immunological competence influences the progression of cervical intraepithelial neoplasia (CIN) to invasive cancer. Information on the local immunological changes during the natural course of CIN is central for the development of new therapies. This study defines the populations of tissue-infiltrating immune cells in a cross-sectional cohort of different grades of CIN and also in a longitudinal cohort of regressing, persistent and progressing low-grade (LG)-CIN. A cohort of 125 women with LG cytological atypia was recruited, of which 64/125 (51%) women with LG-CIN were followed prospectively for 1 year. Paraffin-embedded entry and exit cervical biopsies were used for immunohistochemistry analysis (CD4, CD8, CD56, FOXP3, CD1a and granzyme B). At recruitment, 74/125 (59%), 39/125 (31%) and 12/125 (10%) women referred with LG smears had histologically proven LG-CIN, high-grade (HG) and normal biopsies, respectively. Seventeen of 64 (24.6%) women with LG-CIN progressed to HG-CIN within 1 year. In both LG-CIN and HG-CIN, the predominant intraepithelial cell population were cytotoxic T cells, while CD4+ and FOXP3+ T cells predominated the stromal compartment. Women with LG-CIN who later on regressed displayed a significantly higher number of cytotoxic (granzyme B+) cells in their entry samples. In addition, the ratio between CD8+ cells and granzyme B+ cells was close to 1, suggesting that all infiltrating CD8+ T cells were highly active. In contrast, this ratio was three-fold lower in women, in whom the lesions persisted or progressed. This study suggests that the early infiltration of lesions by highly cytotoxic effector cells protects against progression.

Is colposcopy needed following laser ablation for dysplasia?

To evaluate the effectiveness of cytology and colposcopy in the follow up of women treated by laser CO(2) ablation for cervical intraepithelial neoplasia (CIN). A retrospective analysis of 1784 patients with CIN treated with laser CO(2) ablation from 1998 to 2003 at the Royal Women's Hospital, Melbourne. Data were collected prospectively in a computerised colposcopy database utilised in the Dysplasia Unit. There was equal distribution in the study population treated for low-grade intraepithelial neoplasia (LSIL) and high-grade intraepithelial neoplasia (HSIL), with no significant age difference in both groups (mean 27.6 years). The success rate of treatment of LSIL (94%) was similar to that of HSIL (92%). Fifty-seven per cent of all failures occurred within the first year of treatment. Colposcopy was more sensitive in detecting intraepithelial neoplasia (SIL) than cytology, whereas cytology was more specific. No case of cancer was diagnosed on follow up. CO(2) laser ablation was equally effective in treating different grades of CIN. There is a continuing incidence of recurrent CIN, even up to five years after initial treatment, which suggests that it is necessary for patients to adhere to long-term follow up. The combination of cytology and colposcopic assessment is essential for surveillance of SIL in the initial two years after treatment.

Computerized measurement of intercapillary distance using image analysis in women with cervical intraepithelial neoplasia: correlation with severity

Computerized measurement of intercapillary distance using image analysis in women with cervical intraepithelial neoplasia: correlation with severity

The frequency of bacterial and yeast infection in women with different grades of cervical intraepithelial neoplasia (CIN)

Objective: To determine bacterial and yeast infection of the uterine cervix in women with different grades of cervical intraepithelial neoplasia (CIN). Study design: 578 patients with CIN were included in this study. In order to determine the presence of bacterial and yeast infection, a cervical swab was obtained before conization of the uterine cervix. After surgery and the definitive histology report, the frequency of bacterial and yeast infection in different grades of CIN was calculated. Results: Among 578 patients with CIN, bacterial or yeast infection was present in 379 (65.6%) patients. In patients with CIN 1, infection was present in 20 (71.4%), in CIN 2 in 106 (69.7%) and in CIN 3 in 252 (63.3%) cases. The differences in the frequency of infection among all three groups are not significant. Conclusion: In patients with CIN bacterial and yeast infection of the uterine cervix is very common. Its occurrence does not depend on the grade of CIN.

Human papillomavirus (HPV) in an Icelandic population: correlation of HPV DNA to cyto- and histopathologic lesions and evaluation of treatment strategies

This study is based on 100 cases with cervical intra-epithelial neoplasia (CIN) smears referred for colposcopy and 200 controls with normal smears. The study analyses (a) the frequency of different grades of CIN and koilocytotic lesions among the cases based on cyto- and histopathologic findings; (b) the frequency of human papillomavirus (HPV) among the cases with Virapap/Viratype (V/V) in biopsies vs swabs and among the controls with V/V and polymerase chain reaction (PCR) in swabs; (c) the frequency of the HPV types according to the grade of CIN. Among the cases koilocytotic lesions were found in 98% of the biopsies and 27% of the smears. High-graded smears and high-risk viruses had at entry a positive predictive value (PPV) of 80% and 88% respectively and a sensitivity of 72% for histologically verified high-graded CIN lesions. Both tests combined increased the sensitivity to 88%. The false-negative rate of colposcopy was 3% and the undergraded rate of CIN I and unclassified CIN smears for histologically verified CIN II–III was 62%. Among the cases the rate of HPV positive tests increased with a higher CIN grade. Cytology and colposcopy are complementary for the diagnosis of CIN and the swabs and biopsies for the diagnosis of HPV. Among the cases the rate of HPV-positive tests with V/V was 62% (97% high-risk viruses) and among the controls 5.5% (78% high-risk viruses). Among the controls the frequency of HPV occurrence with PCR was 11.2% and decreased with older age. The therapeutic conclusions are that the high-graded CIN lesions should receive ablative treatment irrespective of HPV typing, whereas low-graded lesions with high-risk viruses should be treated or observed closely.

Outcome of cryosurgery for cervical intraepithelial neoplasia in a developing country

Over a 2-year period cryosurgery was used to treat 73 women who were diagnosed by colposcopy and histologic studies to have cervical intraepithelial neoplasia (CIN). Follow-up was achieved for 70% at 5 years, a significant attendance rate in a developing country. The primary cure rate was 88.5% at 1 year and 90% at 5 years (excluding those lost to follow-up) in all patients with different grades of CIN. The therapy was free of major complications and we found no adverse effect of cryosurgery on subsequent reproductive function in those desiring pregnancy. We conclude that cryosurgery has gained wide acceptance in our geographic area particularly because of its low cost, efficacy and preservation of fertility. For these reasons we would strongly recommend its use provided adequate attention is paid to meticulous pretreatment evaluation and long-term follow-up after therapy.

Stereological estimates of nuclear volume in squamous cell carcinoma of the uterine cervix and its precursors

Using modern stereology, this study was carried out to obtain base-line data concerning three-dimensional, mean nuclear size in precancerous and invasive lesions of the uterine cervix. Unbiased estimates of the volume-weighted mean nuclear volume (nuclear vv) were obtained by point-sampling of nuclear intercepts in 51 pre-treatment biopsies from patients with invasive squamous cell carcinomas (SCC). Vertical sections from 27 specimens with cervical intraepithelial neoplasia (CIN) grades I through III were also investigated, along with 10 CIN III associated with microinvasion (CIN III + M). On average, nuclear vv was larger in SCC than in CIN III and CIN III + M together (2 P = 8.9 . 10(-5). A conspicuous overlap of nuclear vv existed between all investigated lesional groups. The reproducibility of estimates of nuclear vv in biopsies with SCC was acceptable (r = 0.85 and r = 0.84 in intra- and inter-observer studies, respectively). The efficiency of the sampling scheme was high, with more than 60% and more than 80% of the total observed variance contributed by differences between individual lesions with CIN and SCC, respectively. Estimates of nuclear vv based on sampling within the whole epithelial thickness and on sampling in the lower one-third in CIN I and the lower two-thirds in CIN II lesions were of the same magnitude. Approximate estimates of the absolute variation of nuclear vv were directly proportional to individual estimates of nuclear vv, whereas the relative variation of nuclear vv tended to decrease with increasing mean nuclear volume. Based on the rather small number of cases investigated, estimates of nuclear vv are unable to distinguish between different grades of CIN. However, the estimation of nuclear vv is well-suited for the purposes of objective grading of malignancy in SCC.

Carbon dioxide laser management of cervical intraepithelial neoplasia

In this report we describe the use of the carbon dioxide laser for the outpatient management of cervical intraepithelial neoplasia (CIN). A comparison of treatment effectiveness for different grades of CIN is also included. Two hundred fifty-six cases were evaluated by colposcopy, cytology, and histopathology, treated by at least 5 to 6 mm of laser vaporization, and followed up for an average of 10.7 months. Follow-up examinations included cytology, colposcopy, and directed biopsy if a suspicious lesion was discovered. During the follow-up, 18 cases of persistent CIN were identified (7.0%). Most of these were successfully managed with repeat laser treatment. Overall success of laser surgery for CIN, one or two applications, was 97.6%. Few complications were encountered. Laser surgery appears to offer acceptable treatment effectiveneas, early identification of persistent disease, and easy retreatment when required.