Squamous Intraepithelial Lesions Of Cervix Research Articles

Analysis of vaginal microbiota before and after treatment of high-grade squamous intraepithelial lesions of the uterine cervix.

HPV infection is considered the most common sexually transmitted virus today. The persistence of HPV is the main cause for the development of precursor lesions and cervical cancer. There are environmental and non-environmental factors that contribute to the persistence of the virus. Studies indicate a possible relationship between the vaginal microbiota (environmental factor) and the risk of high-grade cervical squamous intraepithelial lesions and cervical cancer. This study evaluates the association between the type of vaginal microbiota and the occurrence of high-grade squamous intraepithelial lesions of the cervix. Observational, longitudinal, prospective, and analytical studies carried out between 2019 and 2021, which evaluated the vaginal microbiota of patients diagnosed with high-grade cervical squamous intraepithelial lesion before and after treatment in two collections with an interval of 6 months, using scrapings and vaginal swabs. In Group I (with lesions) 28 women participated and 29 in Group II (without lesions). According to Nugent, in the initial collection of Group I, 16 women (57%) had lactobacillary microbiota, eight (28%) intermediate, and four (14%) coccus. In Group II, twenty-one (75%) were lactobacillary, one (3%) was intermediate, and seven (24%) werecoccus. With p=0.03. According to Nugent's criteria, there was an association between the type of vaginal microbiota and the occurrence of high-grade cervical squamous intraepithelial lesions of the cervix. The same was not observed in the Donders classification. Studies with a larger sample are needed to confirm our results.

Oxysterol 25-hydroxycholesterol activation of ferritinophagy inhibits the development of squamous intraepithelial lesion of cervix in HPV-positive patients

Squamous intraepithelial lesion of cervix (SIL) in human papillomavirus (HPV)-positive patient often undergoes a silent and long-course development, and most of them with high-grade transit to cervical squamous cell carcinoma (CSCC). The oxysterol 25-hydroxycholesterol (25-HC) is associated with HPV inhibition, autophagy and cholesterol synthesis, however, its function in this long process of SIL development remain unclear. In this study, we demonstrate that 25-HC generation is inhibited through HSIL-to-CSCC transition. The 25-HC activates ferritinophagy in the early stage of SIL, promoting the vulnerability of HSILs to ferroptosis. Therefore, maintaining 25-HC level is crucial for suppressing HSIL progression and holds promise for developing novel clinical therapies for CSCC.

Value of p16 Expression in the Detection of High-Grade Squamous Intraepithelial Lesion of Cervix

Background: Cervical intraepithelial neoplasia (CIN) is usually a precancerous condition but, if left untreated, can develop into invasive cervical cancer. CIN2 and CIN3 are combinedly termed high-grade squamous intraepithelial lesions (HSIL). There are few screening tests based on cytology in detecting HSIL, but they are mostly less accurate. There is over-expression of p16 in pre-cancer and cancer of the cervix. The purpose of this study was to determine the value of p16 expression in the detection of HSIL. Methods: It was a cross-sectional study conducted in the colposcopy clinic of the Department of Obstetrics and Gynecology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from October 2021 to March 2022. The study included 72 HSIL patients detected by colposcopy and had subsequent cervical biopsy and p16 immunohistochemistry. Results: Majority (45.8%) of the patients were found within the 30-39 years age group, 44.4% of the participants were illiterate, and 76.4% came from the middle-income group. Colposcopy-directed cervical Punch or Loop electrosurgical excision procedure (LEEP) biopsy revealed that 70.5% of patients had HSIL, and the rest (64.3%) suffered from LSIL. Positive p16 results were significantly higher among the HSIL group (84.1%) compared to those other than the HSIL group (3.6%) (p<0.001). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the p16 in the detection of HSIL were 84.1%, 96.4%, 79.4%, and 88.9%, respectively. Conclusions: Immunohistochemistry for p16 has a high diagnostic value in detecting HSIL patients. Therefore, this could be recommended for appropriate management of patients with CIN to avoid misdiagnosis and the over or under-treatment.

Detection of Candida albicans in the screening of cervical cancer in rural population of Lucknow

Background Study of Candidal infection is very essential in rural women who being illiterate and financially weak are not aware of personal genital hygiene and thus harbour persistent vaginal infections due to poor availability of medical amenities. Method Rural cervical cancer screening is in progress in the western region of Lucknow, India since May 2013 through camp approach and till date, a total of 2949 women have been cytologically examined. Candidal infection has been observed in the 143 cervical smears of women and findings have been analyzed in relation to the different predisposing factor of cervical carcinogenesis. Result The incidence of Candida albicans seen in cervical smears of the total 2949 women examined was found to be 4.8% which is much higher than in their urban counterparts (1.2%). The Candida was seen more in the inflammatory smears (9.4%) and those showing squamous intraepithelial lesions of cervix (SIL). – (8.2%). The fungus was found more prevalent in the reproductive age group and women complaining of vaginal discharge and was result of persistent vaginal infections in the rural women which should be treated. The Candida was commonly seen in erosion cervix cases but its incidence was high in women with cervicitis and cervix bleeds on touch. Conclusions This persistent vaginal infections were seen in the illiterate and poor rural women who are not aware of personal genital hygiene. There is a need to create awareness for personal genital hygiene through health workers for making any cancer screening program meaningful and successful.

Detailed analysis of different risk factors of cervical cancer including HPV infection at different stages of follow up of squamous intraepithelial lesions of cervix (SIL) in rural women

Background: As situation regarding carcinoma cervix is still alarming in rural population of India, the management of HPV infection and other risk factors contributing to the development of cervical cancer might play a great role in checking the incidence of the disease. Methods: Rural cervical cancer screening is in progress since May 2013 in the western rural region of Lucknow through camp approach and till date, follow up is available in 264 of the totals 498 Squamous Intraepithelial Lesions of Cervix (SIL) showing regression (204) and persistence of the lesions (60). The risk factors including HPV infection have been studied in detail at different stages of follow up in these two groups. Results: Number of risk factors as obvious showed decline in the regressed cases with subsequent follow up which was lacking in the persistent group. Individually, young age factor showed decline with subsequent follow up while multiparity has been found prominent risk factors in both the groups at all stages of follow up. It was seen that the regression rate was high in women above the age of 30 years with multiparity. The decrease in number of vaginal discharge and erosion cervix cases was also found associated with regression of SIL. Conclusion: The risk factors can predict the biological behavior of SIL towards the progression or regression of the lesions and lead to the better management of any cancer screening program. This will also reduce the follow up burden and treatment costs and will thus enhance the overall acceptability at rural level.

Our seven years experience of rural cervical cancer screening in Lucknow, India

This study was undertaken with aim to create awareness among rural women regarding hazards and risk factors of carcinoma cervix and offering single life time cytological screening for early detection of the disease. This was essential as majority of the rural women were illiterate and have poor personal genital hygiene. The present screening program was planned through organizing camps by counseling and motivating 100 women from each village for undergoing Pap smear examination. During last 7 years, a total of 186 camps have been organized in three Blocks of Lucknow, India and 2949 of the 5286 women attending the camps underwent Pap test. Cytological findings were analyzed in these 2949 women in relation to different risk factors of the disease.The squamous intraepithelial lesions of cervix (SIL) were seen in 498 cases (16.8%) while atypical squamous epithelial changes of unknown significance (ASCUS) were observed in only 234 (8.2%). The SIL incidence was found high for all risk factors of cervical cancer like young age, multiparity and vaginal discharge. Candida albicans was found more common and associated with inflammatory and SIL conditions of cervix.The organization of rural cervical cancer screening programs through camp approach and offering single life time cytological examination of cervical smears in rural women may prove very effective in the detection of large number of SIL cases, the adequate treatment of which will check the progression of the disease and minimize the incidence of carcinoma cervix and associated mortality in rural India.

Significance of inflammation in cervical cytology smears in rural women of India: An observational study

Introduction: Inflammatory smears are frequently seen in cervical cancer screening and they have been widely implicated as precursor of premalignancy of cervix. In the present study, attempt has been made to find out correlation between inflammation and different predisposing factors to cervical carcinogenesis in the rural context. Materials and Methods: Cervical cancer screening is in progress in the rural population of West Lucknow, India since May 2013 under the auspices of Era’s Lucknow Medical College and Hospital, Lucknow, India and till March 2018, cervical smears of 2563 women have been cytologically examined. Results: The incidence of inflammation was found to be 33.7% in the present series. It was non-specific in 91.3% and was associated with either Candida albicans or Trichomonas vaginalis in 8.2% of cases. The inflammation was associated with low grade squamous intraepithelial lesions of cervix (LSIL) in 176 cases (20.1%) which were mostly asymptomatic (36.1%) and some had cervical lesions on the cervix (11.2%). The inflammatory smears were mostly seen in women complaining of vaginal discharge (47.1%) or vague pain in the lower abdomen (31.9%). The inflammation was more common in younger sexually active women between 21-40 years and was seen rising with increasing parity. Conclusion: The accumulated data points out that the clinical lesions of cervix and multiparity have some impact in the initiation of inflammatory changes in the cervical epithelium. The inflammatory smears, whenever, reported should be adequately treated and smears are repeated after 6 months to rule out any persistence of inflammation or development of any premalignancy. Keywords: Inflammation, LSIL, STDs, Rural women.

CERVICAL CANCER SCREENING IN RURAL WOMEN POPULATION OF LUCKNOW WEST, INDIA: PROBLEMS AND BENEFITS

Carcinoma cervix is a major health problem faced by Indian women and situation is very alarming in rural population because of illiteracy and poverty. There is urgent need of creating awareness regarding the risk factors of cervical cancer such as early marriage and multiparity in the rural women and the importance of early detection of the cervical cancer. With aim for providing single life time Pap smear cover to the rural women, cervical cancer screening program was initiated in May 2013 by Era's Lucknow, Medical College and Hospital, Lucknow, through organizing camps in the villages of Lucknow ,west. Till December 2019, a total of 183 camps have been organized and 5209 women attended these camps (28.5%). Pap smear examination could be done in only 2912 women (55.9%). The incidence of squamous intraepithelial lesions of cervix (SIL) was found to be very high in these women (17.1%) though majority of SIL were of low grade (LSIL). This may be related to the poor personal genital hygiene prevailing in rural women due to illiteracy. In the present review, the SIL incidence has been extensively analyzed in relation to different predisposing factors of cervical carcinogenesis and problems faced during camp organization and the benefits derived from these camps to rural women have been highlighted.

Different Risk Factors Associated with Persistence or Regression of Squamous Intraepithelial Lesions of Cervix under Rural Conditions in India

Introduction: In many Human Papilloma Virus (HPV) negative women, the Squamous Intraepithelial Lesions (SIL) of cervix often show persistence or progression of the lesion on follow-up which shows involvement of other risk factors of carcinoma cervix. Aim: The aim of the study was to evaluate the different risk factors of cervical cancer in persistent, progressed and regressed cases of SIL to identify the prominent ones among them. Materials and Methods: The study had been of a screening type for early detection of cervical cancer and it was done in the women population of west Lucknow, Uttar Pradesh, India (May, 2013-February, 2020). Cervical smears were collected in 2949 women attending the camps whose cytological examination revealed 498 cases of SIL and follow-up was available in 254 of them done through home visits after 1-4 years. Persistence of SIL was seen in 60 women on follow-up while in the remaining 194, the SIL had regressed to normal. The percentage of different risk factors seen with the persistence or regression of SIL was studied. Results: Among the different risk factors identified, prominent were of young age between 16-30 years with vaginal discharge and their percentage were insignificantly higher with persistence of SIL than in the regression group. Multiparity was also highly associated with both persistence and regression of SIL. The erosion of cervix was significantly associated with SIL persistence while associated inflammation was insignificantly higher in persistent than in the regression group. The percentage of all these factors except erosion of cervix was found higher in HPV- positive than in the HPV negative women. Conclusion: It appears that all the identified risk factors are present both in persistent and regression group but their percentage is higher with persistence of SIL. Hence, presence of any of these factors in these two groups should be viewed with caution to rule out any progression/recurrence of SIL.

ASCUS (Atypical Squamous Cells of Undetermined Significance) in the Cervical Smears of Women from Rural Population of Lucknow West.

Though Atypical squamous cells of undetermined significance (ASCUS) are not always precursors of cervical pre-malignancy but they need timely diagnosis and careful periodical follow-up. The present study was carried out to investigate the incidence of ASCUS and SIL (squamous intraepithelial lesion of cervix) in women under rural setting. Cervical cancer screening is in progress in rural population of West Lucknow, India, since May 2013 under auspices of Era's Lucknow Medical College and Hospital, Lucknow, and a total of 2478 women have been cytologically examined till October 2017. The incidence of ASCUS was found to be 8.8%, which was approximately less than half of the squamous intraepithelial lesions of cervix (SIL) rate (17.9%). The ASCUS rate was higher in the symptomatic women (9.4%) than (7.4%) seen in women without symptoms. The ASCUS incidence was higher in younger sexually active group up to 40years after which it declined. The ASCUS rate was higher in all parity groups and was commonly associated with pain in lower abdomen and vaginal discharge. The ASCUS rate was higher with erosion cervix, while the commonly associated sexually transmitted diseases (STD) were found to be Candida albicans (2.4%). Follow-up after 18-24months was available in 40 cases of ASCUS, and progression to low-grade SIL (LSIL) was seen in 7 (17.5%) and to high-grade SIL (HSIL) in one case (2.5%). The findings suggest that the ASCUS are not always precursors of SIL, but they need periodical follow-up after every 6months. This will be ideal management of ASCUS under low-resource settings.

A Rare Case of Cartilaginous Heterotopia in Broad Ligament of Uterus

ABSTRACT Heterotopia is the occurrence of mature tissue at abnormal location. A very rare case of cartilaginous heterotopias in the broad ligament of a 47-year-old female is described. Literature contains very few references related to it. In this patient, there was no evidence of any malignancy in the abdomen or in any other part of the body, except cervical intraepithelial neoplasia changes in cervix. The peritoneal lesion was an incidental finding in this female who underwent total abdominal hysterectomy in view of low-grade squamous intraepithelial lesion of cervix on cervical biopsy. A firm to hard, white-colored, tubular, branched structure, embedded in left broad ligament reaching till serosa of left fallopian tube and undersurface of left ovary was present. Histopathology showed mature cartilage of hyaline type with well-formed chondrocytes and lacunae with surrounding fibrosis with no evidence of cytological atypia, reactive inflammatory changes, or foreign body reaction. This may represent metaplastic lesions of secondary Müllerian system or benign neoplastic lesions (chondroma) of submesothelium. How to cite this article Kaur K, Kaur A, Chopra N, Kaur A. A Rare Case of Cartilaginous Heterotopia in Broad Ligament of Uterus. J South Asian Feder Obst Gynae 2017;9(2):192-194.

Insulin-Like Growth Factor I Receptor (IGF-IR) Ligands and BMI in Squamous Intra-Epithelial Lesion (SIL) of Cervix.

Cancer cervix is the most common cancer in women in developing countries like India. Several studies have linked insulin-like growth factors-I & II (IGF-I and IGF-II) and IGF binding proteins-3 (IGFBP-3) with pathogenesis of Squamous Intraepithelial Lesion of cervix (SIL). To the best of our knowledge, no study has shown any correlation between circulating C-Peptide levels and SIL. The present study has attempted to evaluate the correlation between SIL and IGF-IR ligands (IGF-I, IGF-II, C-Peptide), IGF binding protein (IGFBP-3) and Body Mass Index (BMI). The present case-control study consisted of 31 histologically proven SIL cases and 31 age matched controls without evidence of SIL. A 10 ml blood sample was collected in heparinized vial. Plasma was separated immediately using centrifugation and was stored at -80(0) C till further analysis. Plasma levels of IGF-I, IGF-II, C-peptide and IGFBP3 were measured using commercially available Enzyme Linked Immunosorbent Assay (ELISA) kit. Height and weight was noted for calculation of BMI. Bio-effective molar ratio (BEMR) was calculated as 3.72 x {(0.25 x IGF-I) + (0.032 x IGF-II) + (0.0025 x C-peptide)} / {(1435 + IGFBP-3) - (2.79 x IGF-I) - (2.87 x IGF-II)}. Statistical analysis was performed using SPSS and Microsoft Excel software employing student t-test, Mann-Whitney and Chi-square test for trend while binary logistic regression was used to estimate the odds ratios (OR) and corresponding 95% Confidence Intervals (CI). IGF-I, IGF-II levels and BEMR were significantly increased in SIL compared to controls (p= 0.001, p <0.001, and p <0.001, respectively). C-Peptide levels were higher in controls than SIL (p = 0.04). IGFBP-3 & BMI in SIL were not significantly related when compared with controls. Risk of SIL in 4(th) quartile for BEMR, IGF-I, and IGF-II was 12.18(95% CI= 3.13-47.39), 3.94(95% CI = 1.24-12.56), and 4.57(95% CI = 1.42-14.7), respectively. Elevated levels of IGF-I and IGF-II are associated with risk of SIL while BEMR emerges out to be a derived factor strongly associated with risk of SIL.

Single life time cytological screening in high risk women as an economical and feasible approach to control cervical cancer in developing countries like India.

In view of funding crunches and inadequate manpower in cytology in developing countries like India, single lifetime screening for cervical cancer has been suggested. In this study, an attempt was made to identify high risk groups of women for this screening to make it more effective for early detection. Cytological data were derived from the ongoing routine cervical cytology screening program for women attending Gynaecology Out Patient Department of Queen Mary's Hospital of K.G.Medical University, Lucknow, India during a span of 35 years (April 1971 - December 2005). Cervical smears in a total of 38,256 women were cytologically evaluated. The frequencies of squamous intraepithelial lesions of cervix (SIL) and carcinoma cervix were found to be 7.0% and 0.6%, respectively, in the series. Predisposing factors related to cervical carcinogenesis were analyzed in detail to establish the most vulnerable groups of women for single life time screening. The incidence of SIL and carcinoma cervix was found to be maximal in women above the age of 40 years irrespective of parity and in multiparous women (with three or more children) irrespective of age. The incidence of cervical cytopathologies was significantly higher in symptomatic women, the frequency of SIL being alarmingly higher in women complaining of contact bleeding and that of carcinoma cervix in older women with postmenopausal bleeding. It is consequently felt that single life time screening must include the three groups of women delineated above. Such selective screening appears to be the most economical, cost effective and feasible approach to affordably control the menace of cervical cancer in developing countries like India.

Cervical Cytology Associated with Pelvic Inflammatory Diseases

Objective: The present study was aimed to investigate the incidence of squamous intraepithelial lesions of cervix (SIL), frank cervical cancer and different STDs in 503 women with pelvic inflammatory disease (PID). Study design: Cytological evolution of cervical smears was carried out in 503 women attending Gynae Outpatient Department of Era’s Lucknow Medical College, Lucknow India, between October 2009 and June 2014 who were diagnosed with PID and also during Rural Cervical Cancer Screening in Malihabad and Kakori Block of Lucknow District between May 2013 to April 2015. Results: The cervical cytology in 503 women with PID showed alarmingly high rate of SIL (144- cases -28.6%) though 134 of them were of low grade. No case of carcinoma cervix was seen. The incidence of Candida albicans was 4.3% in these women and only 2 cases of Trichomonal infection were seen. The incidence of SIL was maximum in younger, sexually active women between 21-30 years after which it declined. Conclusion: The study revealed a very high incidence of SIL associated with PID. As majority of the women screened were from rural areas, it appears that poor hygiene and persistent infection has led to the high incidence of SIL. Hence urgent need is felt in organizing cytological screening programme in rural region of the country to screen specially the symptomatic women to detect any early onset of cervical precancer, the subsequent treatment of which would check any progression of the disease to malignancy.

Abstract 4789: Human papillomavirus genotyping in urine samples of women with squamous intraepithelial lesions of cervix.

Abstract Human papillomavirus (HPV) is the most frequent microorganism sexually transmitted and is the causal agent of cervical carcinoma were it could be found in 99.7% of cases. The detection of HPV en women with or without lesions of cervix is generally performed in biopsies and cytobrush, which are invasive samples; therefore many patients do not attend to health care to get HPV test. The aim of this study was to develop a technique capable of detect and genotype HPV in urine samples of women with squamous intraepithelial lesions of cervix. For this study, 87 urine samples from patients with normal epithelia of cervix (25), low grade squamous intraepithelial lesion (LSIL) (24), high grade squamous intraepithelial lesion (HSIL) (38) were collected from women who attended to gynecological care in a public health center in Temuco, Chile. DNA extraction was performed with a manual method. For protein precipitation, Phenol-Chloroform and ammonium acetate were used. DNA precipitation was performed with absolute ethanol. HPV detection and genotyping was performed with the kit HPV Typing (patent pending) which is capable of detect 18 more frequent HPV types and beta globin gen as control of DNA integrity. 20% of urines from normal epithelia women were positive for HPV. Three genotypes were found in normal samples: HPV52, HPV42 and HPV53. LSIL there was a 92% of HPV positivity and the most frequent genotypes were HPV16 and HPV18. In HSIL, 95% of urine sample were positive for HPV. HPV16, HPV18 and HPV31 were the most frequent genotypes in HSIL. Genotypes found in urine samples were similar to world reports. Using the DNA extraction described before and HPV easy typing kit it is possible to detect and genotype HPV in urine samples. These results suggest that is possible a HPV primary screening test in non-invasive sample, complementing PAP smear in order to determinate which women have a higher risk of developing preneoplastic and neoplastics lesions. Grant Support: Proyect CORFO N° 09CN14-5960 (CEGIN). CI is recipient of grants from FONDECYT Postdoctoral Proyect N° 3130630. PB is recipient of grants from FONDECYT Postdoctoral Proyect N° 3120141. Citation Format: Tamara Viscarra, Alejandra Andana, Priscilla Brebi, Doris Menzel, Carmen G. Ili, Ramon Silva, Juan C. Roa, Raul Sanchez. Human papillomavirus genotyping in urine samples of women with squamous intraepithelial lesions of cervix. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4789. doi:10.1158/1538-7445.AM2013-4789

Fractal dimension of chromatin texture of squamous intraepithelial lesions of cervix

The aim of this study was to explore the role of fractal dimension (FD) of chromatin texture in routinely stained Papanicolaou's smears and to distinguish the different grades of cervical intraepithelial lesions and normal cervical cells. We selected 14 each cases of normal, low grade cervical intra epithelial lesions (LSIL), and high-grade cervical intra epithelial lesions (HSIL) of Papanicolaou's stained cervical smears. Fractal dimension of the pseudo three-dimensional grey image of the nuclear chromatin was measured in 140 nuclei of each group. Mean FD of the normal cases, LSIL cases, and HSIL cases were 2.4225 ± 0.06410, 2.5159 ± 0.03291, and 2.5905 ± 0.06840, respectively. ANOVA test showed significant differences of mean FD in all these three groups (P < 0.000). Fractal dimension of the chromatin texture is easy to perform and can be done in routinely stained Papanicolaou's smear. It is reproducible and gives valuable information about the chromatin texture of the nucleus. In future, this promising variable can be incorporated along with other image morphometric features for accurate classification of dysplastic cells in cervical smear.

Methylation of the long control region of HPV16 is related to the severity of cervical neoplasia

Objective Oncogenic human papillomavirus (HPV) is the cause of cervical cancer. Hypermethylation of the CpG islands located at the long control region (LCR) of the HPV genome may regulate the expression of the major oncogenes E6 and E7, and may relate to cancer progression. The goal of the present study was to investigate the methylation patterns of CpG dinucleotides contained within the LCR of the HPV16 genome in a collection of clinical specimens comprising the full spectrum of cervical carcinogenesis. Study design The status of LCR methylation was investigated in HPV16-infected cervical precancer and cancer cell lines, and in HPV16-infected low-grade squamous intraepithelial lesion of cervix (LSIL, n = 17), high-grade squamous intraepithelial lesion (HSIL, n = 21) and invasive squamous cell carcinoma (SCC, n = 15) by bisulfite sequencing. Results Among the three CpG islands of HPV16 LCR, methylation was found in three in the CaSki cell, in two upstream ones in SiHa cell, and none in the precancerous Z172 cell. Reactivation of E6 gene expression upon demethylation by 5-aza-dC and TSA treatments was noted in CaSki cells. In HPV-infected cervical specimens, progressive methylation of HPV16 LCR was noted, with rates of 5.9%, 33.3% and 53.3% in LSIL, HSIL and SCC, respectively ( P < 0.01). A trend toward increasing density of CpG methylation was also noted. Topologically, more methylated sites were found at the E6/E7 promoter region in SCC, compared with LSIL and HSIL. Conclusion The study disclosed downregulation of E6 gene transcription by LCR methylation in cervical cancer cells. Methylation of HPV 16 LCR is highly associated with severity of cervical neoplasm.