Grade Squamous Intraepithelial Lesion Research Articles

Cervical precancerous and cancerous lesions screening using Pap smear test at Provincial Referral Hospital of Bukavu, Eastern DR Congo: profile and recommendations to stakeholders.

cervical cancer is a health concern worldwide. The South Kivu Province in the Eastern DR Congo is facing many cases of this disease but poorly screened and reported. The objective of this was to determine the prevalence of cell abnormalities at cervical cytology in a tertiary teaching hospital in Bukavu and their association with common risk factors of cervical cancer. a cross-sectional study was conducted on 142 women attending the Provincial Referral Hospital of Bukavu (HPGRB) from February to December 2021. Quantitative variables were described by their median following their asymmetric distributions and the qualitative variables in absolute and relative frequencies. Then the Chi-square test was used for the comparison of proportion. forty-five percent of the participants had between three and five children. Twenty-two (15.5%) of the 142 patients reported to have two or more sexual partners and 17.5% reported the use of hormonal contraception. The prevalence of cell abnormalities at cervical cytology was 17% of which Low- Grade Squamous Intraepithelial Lesion (LSIL) was the most representative (12.9%). There was no statistically significant association between the common cervical risk factors and the occurrence of cell abnormalities. cervical pre-cancerous lesions are frequent in South Kivu province. The Pap smear test remains an early and affordable screening method and constitutes a secondary prevention strategy in women of 18 years and older in a low-income country such as DR Congo where vaccination against HPV is still hypothetic.

A Case Report of Spontaneous Regression of grade 3 Clear Cell Endometrial Cancer

Spontaneous remission of cancer (SR) is a rare, defined as a complete or partial, temporary, or permanent disappearance of all or at least some relevant parameters of a soundly diagnosed malignant disease without any medical treatment or with treatment that is considered inadequate to produce the resulting regression. We present the case of a 43-year-old woman who initially received a diagnosis of high- grade squamous intraepithelial lesion (HSIL) on a Pap smear, further examination and MVA (Manual Vacuum Aspiration) curettage biopsy revealing poorly differentiated clear cell adenocarcinoma of the endometrium, stage 1a3 and subclinical hypothyroidism. The patient was prescribed thyroid tablet replacement but chose not to pursue any cancer treatment. Following two consecutive MVA curettage procedures, she returned for a hysteroscopic examination and the third MVA curettage biopsy, the histological report indicated the absence of any malignancy. Throughout the course of her illness, the patient underwent a total of ten sessions of MVA endometrial curettage and received thyroid replacement therapy for her subclinical hypothyroidism. Despite our initial reservations, we continue to provide care and support to her throughout whole course of this illness. We demonstrated that a patient's autonomy in refusing medical treatment is a fundamental ethical and legal principle in healthcare. Conclusion: We report the 8 cases of spontaneous remission (SR) in endometrial cancer. Given the infrequent occurrence of such cases, it is imperative to involve in a comprehensive and in-depth discussion.

Results of total vaginal hysterectomy in patients with cervical intraepithelial neoplasia

Abstract Introduction: Cervical intraepithelial neoplasia (CIN) is considered a precancerous lesion and is usually treated aggressively. Total hysterectomy is indicated in some cases and can be performed through the abdomen, vaginally, through laparoscopic surgery and robotic surgery combined with laparoscopic surgery. It is necessary to study to evaluate the effectiveness of total vaginal hysterectomy. Patients and methods: Clinical non-controlled interventional study in 32 patients with high - grade squamous intraepithelial lesions who underwent a total vaginal hysterectomy at Department of Oncology and Palliative Care at Hanoi Medical University Hospital from August 2018 to May 2021. Results: The average age in the study was 48,9 years old,mainly in the age group < 44 years old, accounting for 37,5%. The majority of patients came to the clinic because of vaginal discharge. All patients had a detailed clinical examination, gynecological ultrasound, PAP test, cervical biopsy to confirm the diagnosis before surgery. The average surgery time was 55,9±14,9 minutes, and the average volume of blood loss was 76,8 ± 23,5ml. Post-operative patients recover movement soon, the level of pain is reduced. There was none of case with intra- and postoperative complications were recorded. During the follow-up process, no vaginal intraepithelial neoplasia and abdominal lymphadenopathy recurrence was detected. Conclusion: Total vaginal hysterectomy in patients with high grade squamous intraepithelial lesion is considered as safe and feasible. Key words: Cervical intraepithelial neoplasia, total vaginal hysterectomy. Human papiloma virus.

A CASE OF CERVICAL INTRAEPITHELIAL NEOPLASIA - MANAGEMENT THROUGH AYURVEDA

Introduction – Cervical cancer is the 2nd most leading prevalent cancer in India. There are an estimated 123,000 new cases of cervical cancer in India every year with 67,000 deaths in women alone. Cervical cancer in Recent studies shows that screening of cervical cancer reduces the disease incidence and disease mortality by 50%. Low- grade squamous intraepithelial lesion (LSIL) is a common abnormal result on a Pap smear cervical test. It’s also known as mild dysplasia. Methodology – Here is a case report of a patient aged 26yrs with complaints of white discharge per vagina with severe itching, on routine cervical screening investigations found to have Low grade squamous intraepithelial neoplasms. She was treated with Ayurvedic sthanika chikitsa (Local therapies) such as Yoni prakshalana (Vaginal douching), and Yoni pichu (Vaginal tamponing) for 7 days along with shaman chikitsa. Later PAP smear was repeated after 1 month of follow up and found to have negative for intraepithelial neoplasia. And there was relief in the symptoms following treatment. Results- In this case, there was a relief of symptoms and on follow up when Pap smear was repeated, there was negative for intraepithelial neoplasia. Ayurvedic treatment modalities such as Sthanika chikitsa which includes yoni prakshalana and Yoni Pichu are the line of treatment for various gynecological problems and help in reducing mortality and morbidity caused due to cervical cancer in India. Discussion- Here Low-grade squamous Intraepithelial neoplasia can be considered as the Sanchaya avastha and hence diagnosing the disease in its Sanchaya avastha i.e mild dysplasia, is important. During Sanchaya avastha there is localized neoplastic changes of cervical cells and there is Manifestation of Low-grade Intraepithelial Neo- plasia. In the later stages of Kriyakala (Stages of disease manifestation) the neoplasia turns into metastasis and further differentiation occurs which Manifests all the symptoms of Cervical Cancer. Hence treatment modalities such as Yoni prakshalana and yoni pichu helps in preventing later conditions such as cervical cancer. Keywords: Cervical Cancer, LSIL, Ayurveda, Sanchaya

Biochemical Mechanisms of Action of Natural Ingredients from the Vaginal Applicators for the Management of Preinvasive Cervical Lesions

A successfully implemented screening program for cervical cancer is essential for detecting cervical intraepithelial lesions which offer the possibility of appropriate management and monitoring, implicitly the limitation of the progression to an invasive form of cancer. For different grades of squamous intraepithelial lesions, the use of vaginal tablets or applicators based on various natural substances as hyaluronic acid, beta-glucan and Coriolus Versicolor is possible with the purpose of expectative management or prior and post excisional intervention. We present the incidence trend of abnormal Pap smear results for the last five years in the University Emergency Hospital of Bucharest, with a summary of the literature regarding the biochemical mechanism of the main natural components from vaginal tablets used in the management of precancerous cervical lesions HPV induced and we share our personal experience with three clinical cases that benefited from this therapy. As there is a therapeutic window between the Pap-smear result, colposcopy and preparing for intervention, local treatment with natural components is a suitable choice as it is easy to use, inexpensive and efficient. The conclusion we reached is that the vaginal treatment with natural substances can be useful in terms of improving the local inflammatory process on the one hand and lubricating and regenerating tissues with the improvement of subsequent procedural performance on the other.

Comparative measurement of D- and L-lactic acid isomers in vaginal secretions: association with high-grade cervical squamous intraepithelial lesions

Identification of low-cost protocols to identify women at elevated susceptibility to develop cervical intra-epithelial abnormalities would aid in more individualized monitoring. We evaluated whether quantitation of the D- and L-lactic acid isomers in vaginal secretions could differentiate women with normal cervical epithelia from those with a low (LSIL) or high (HSIL) grade squamous intraepithelial lesion or with cervical cancer. Vaginal samples, collected from 78 women undetgoing cervical colposcopy and biopsy, were tested for pH, bacterial composition by Gram stain (Nugent score) and concentrations of D- and L-lactic acid by a colorimetric assay. Subsequent diagnosis was 23 women with normal cervical epithelium, 10 with LSIL, 43 with HSIL and 2 with cervical cancer. Vaginal pH and Nugent score were comparable in all subject groups. The concentration of L-lactic acid, but not D-lactic acid, as well as the L/D-lactic acid ratio, were significantly elevated (p < 0.01) in women with HSIL and cervical cancer. Comparative measurement of vaginal D- and L-lactic acid isomers may provide a low-cost alternative to identification of women with an elevated susceptibility to cervical abnormalities.

Sequential Application of Lugol's Iodine Test after Acetic Acid for Detecting Cervical Dysplasia: A Prospective Cohort Study.

Applying Lugol’s iodine solution to the cervix followed by colposcopic assessment is an established standard test to identify low grade/high grade squamous intraepithelial lesions (LSIL/HSIL). Here, we assessed the performance of Lugol’s iodine test during colposcopy using a standardized protocol with 5% acetic acid followed by 5% Lugol’s iodine solution and recording the most severe acetowhite (MSAWL) and iodine-negative (MSINL) lesions in a prospective cohort of consecutive women referred to our specialized colposcopy unit. The primary study endpoint was the sensitivity/specificity of MSINL for the detection of LSIL/HSIL. Secondary endpoints were the time to first appearance of the MSINL, MSINL staining intensity, and fading of MSINL. Three hundred and twenty women were included. The sensitivity and specificity of MSINL for the detection of LSIL/HSIL was 81.4 (95%—confidence interval (CI) 77.3–85.0)% and 29.5 (24.2–35.5)%, respectively. Ninety-six MSINL were identified exclusively by Lugol’s iodine test (no pathology, n = 46; LSIL, n = 29; HSIL, n = 21) (number needed to biopsy to identify one additional LSIL/HSIL = 1.9). In 17/320 (5.3%) patients, the clinical management was changed based on the result of Lugol’s iodine test. Video analysis showed an instant appearance of the MSINL within 10 s in 100% of cases. Intensity of MSINL significantly correlated with the presence/absence of LSIL/HSIL (Spearman rank order correlation; p < 0.0001). Fading of iodine-induced staining intensity over time was not observed. Thus, Lugol’s iodine showed moderate sensitivity and poor specificity, but changed clinical management in 5% of cases when used in addition to acetic acid.

Prevalence of Human Papilloma virus in women with Abnormal Cervical Smears from Sarawak, Malaysia

Introduction: Cervical cancer is common cancer and ranked in fourth place in both incidence and mortality worldwide. It is 3rd most common female cancer in Malaysia with a lifetime risk of 1 in 116. Infection with high-risk oncogenic human papillomavirus (HPV) is recognized as one of the substantial risk factors for the development of cervical cancers. Methods: It was a cross-sectional study conducted to determine the prevalence of HPV infection and its subtypes among women with various degrees of abnormal smears, who were seen in the colposcopy clinic of Sarawak General Hospital within six months’ period from January to June 2018. We recruited 56 participants. There were 23 each for an atypical squamous cell of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) and 10 high- grade squamous intraepithelial lesion (HSIL). DNA was extracted, and HPV genotypes were determined via polymerase chain reaction (PCR) using two primer pairs MY09/MY11 and GP5+/GP6+. Results: The age ranged from 23 to 56 years, with a mean age of 42.96 years. HPV was detected in 20 out of 56 (35.7%). There were 6 high-risk oncogenic HPVs (18, 51, 52, 56, 58, 68) detected in participants and the most prevalent subtypes were 18, 52, and 58 (20% each). Four low-risk HPVs detected were 6, 53, 70, and 84. There was a significant association between the severity of cervical lesions and HPV positivity (P &lt; 0.004). HSIL had the highest positive predictive value to have HPV infection as 70% compared to 43.4% of LSIL and 9.3% of ASC-US. Conclusion: Distribution of HPV subtypes from women with abnormal smears from Sarawak indicated a high prevalence of HPV 18, 52, and 58. We also identified HPV 70, which has never been reported in West Malaysia. These findings could contribute valuable information for HPV vaccination strategies, particularly for Sarawakian women.

MicroRNAs expression changes coincide with low or high grade of squamous intraepithelial lesion infected by HPV-16

Cervical cancer is the second most common malignancy worldwide and the third leading cause of death in women. It accounts for 1% of all cancers and is the third neoplasm ever diagnosed. Several viruses can cause cancer so that viruses are connected to almost 15–20% of human malignancies and nearly 80% of cervical and liver. MicroRNAs can be used as a tumor oncogene by controlling related genes of tumors. In addition, they can be applied as biomarkers in the diagnosis, prognosis, and even treatment of cancer tissues. The current study aimed to investigate the changes in the expression of miR-21, miR-16, miR-143, and miR-34a related to the severity of the disease in women with low or high grades of squamous intraepithelial lesion or carcinoma infected by HPV-16. In this case-control study, the expression of four microRNAs in formalin-fixed paraffin-embedded tissues of 36 patients with cervical cancer and 36 samples of healthy women are studied by real-time-PCR. For all four miRNAs, enhanced expression was observed in low-grade SIL patients, compared to controls. Also, increased expression of miR-21 in high-grade SIL patients and decreased expression of miR-143 in this grade were found. MicroRNAs can play important roles as biomarkers in the diagnosis of different stages of cervical carcinoma.

Les néoplasies intraépithéliales vulvaires

Vulvar squamous cell carcinoma arises from precursor lesions: vulvar intraepithelial neoplasias (VIN). Most of them are caused by the human papillomavirus (HPV), and the precursor lesion for this group is VIN usual type/high grade squamous intraepithelial lesion (uVIN/HSIL) of variable clinical presentation and having a light invasive potential. Some VIN are HPV-independent and arise in older women against the background of chronic dermatoses, mostly lichen sclerosus. Their histological diagnosis is more subtle. They have a higher invasive potential. A third precursor, leading to well-differentiated, or even verrucous, carcinomas, is still ill-defined to this day. We detail these lesions' clinics, histology, and biomarkers (immunohistochemical and molecular).

P16 Immunostaining Can Eliminate Approximately 20% Inaccurate Diagnosis of Low-Grade Squamous Intraepithelial Lesions (SIL) in Cervical Biopsies

Abstract Introduction/Objective Differentiating low-grade SIL from reactive changes on light microscopy has remained controversial. P16 immunostaining is widely accepted in high-grade SIL unlike in low-grade SIL. We focused on the use of p16 immunostaining in eliminating inaccurate diagnosis of low-grade SIL on light microscopy. Methods A retrospective study on 60 cervical biopsies results over a 2 year-period was conducted using 35 suspicious cases for low-grade SIL (bi-nucleation and some nuclear atypia) and 25 low suspicion cases (enlarged nuclei but nuclear atypia cannot differentiate from reactive changes). All cases were stained for p16, significant nuclear expression of p16 was determined as low- grade SIL. Results After p16 immunostaining, 30/35 (85%) cervical biopsies from the suspicious group were found to be truly positive for low-grade SIL while 5/35 (15%) biopsies negative for p16 immunostaining were regarded as reactive changes. In the low suspicious group, 7/25 (28%) were found to be positive for low-grade SIL and 18/25 (72%) biopsies were negative, favoring reactive changes. The overall percentage of all 60 biopsies that showed a changed diagnosis based on p16 immunostaining was 20% (5 were truly negative in the suspicious group and 7 were truly positive in the low suspicious group). Using a 2 x 2 table with p16 as a gold standard for all biopsies, sensitivity and specificity of light microscopy for low-grade SIL were only 81% and 78% respectively. Conclusion Our study showed that p16 immunostaining can also be utilized to eliminate inaccurate diagnosis of low- grade SIL up to 20% in cervical biopsies.

Patterns of Cytokeratin 7 Expression in Cervical Squamous Intraepithelial Lesions

Abstract Introduction/Objective It has been suggested that cervical high-grade squamous intraepithelial lesions (HSIL/CIN2-3) arise from squamocolumnar junction cells that express cytokeratin 7 (CK7). Significant CK7 expression (gradation or full-thickness) has been proposed as a marker of progression of low-grade squamous intraepithelial lesions (LSIL/CIN1) to HSIL and of persistence of HSIL/CIN2. The goal of the study is to survey patterns of CK 7 expression in the different grades of squamous intraepithelial lesions (SILs). Methods 65 cervical specimens (biopsies and excisions) containing 95 lesions of different grades were assessed by immunohistochemical analysis (IHC) for CK7 expression. 26 cases contained more one lesion grade. The diagnosis of HSIL (CIN2-3) was confirmed by p16 IHC. CK7 expression was scored negative, patchy, gradation (i.e., top-down), or full-thickness pattern. In cases with heterogeneous staining, the strongest pattern was used for analysis. Results There was significant variation in patterns within morphologically contiguous lesional foci; staining heterogeneity was noted in 42% of cases. All patterns of expression were encountered in all lesion grades. LSIL/CIN1 (n=47), either alone (n=27) or in combination with HSIL (n=20), often lacked CK7 expression (53%) or were patchy (17%). The frequency of significant (gradation or full-thickness) CK7 expression in LSIL with concomitant HSIL was greater than LSIL occurring alone (40% vs. 22%, respectively). HSIL/CIN3 (n=19) was dominated by full-thickness expression (57%). HSIL/CIN2 (n=29) had a very heterogeneous spectrum of expression with 34% of cases lacking expression. Conclusion CK7 expression is variable across all grades of SILs. LSIL with concomitant HSIL was associated with significant CK7 expression more frequently than LSIL alone. Significant proportion of HSIL, particularly CIN2, lacks CK7 expression. Given this variability, caution is advised regarding the use of CK7 expression as a marker of progression.

PD-1/PD-L1 expression in anal squamous intraepithelial lesions.

Introduction: Studies have shown that the PD-1/PD-L1 immunomodulatory pathway slows down anti-tumor immunity in a number of cancers. The description of the expression of these molecules has never been performed in anal low-grade/high grade squamous intra-epithelial lesions (LSIL/HSIL respectively).Materials and Methods: Patients followed in the AIN3 cohort were routinely sampled. For each selected sample, an immunohistochemical study was performed with anti-CD8, PD-1, PD-L1 antibodies. The presence and distribution of CD8+ lymphocytes, and the presence of PD-1+ lymphocytes and PD-L1+ epithelial cells were assessed. The comparison of these characteristics was performed between the HSIL and LSIL groups.Results: 33 patients were included and 78 samples selected (60 HSIL and 18 LSIL). CD8+ lymphocytes were observed more frequently in HSIL versus LSIL in the lamina propria or intra epithelial (respectively 90% vs. 60%, p = 0.01; and 62% vs. 33%, p = 0.04). PD-1+ lymphocytes were observed more frequently in HSIL versus LSIL (41% vs 11%, p = 0.03). There was no difference between HSIL and LSIL for PD-L1+ epithelial cells.Conclusions: Anal dysplastic lesions are accompanied by an inflammatory lymphocytic infiltrate expressing CD8 and PD-1, more frequent in high-grade lesions. These results highlight the involvement of the PD-1/PD-L1 pathway in the natural history of anal dysplasia.

Integrated Non-invasive Management of Cervical Low-Grade Squamous Intraepithelial Lesions Observed in Papanicolaou Smears with Antimicrobials Followed by Oral Curcuma Longa Extract

Background: Prevention of cervical cancer by treatment of precancerous conditions is critical in saving lives and is cost-effective. Turmeric bio-actives have shown potential anticancer activity in vitro, in vivo and in early clinical studies. The activity and safety of non-invasive integrated treatment with antimicrobials and oral turmeric extract was explored clinically in women with Low – grade Squamous Intraepithelial Lesion (LSIL) detected in Papanicolaou (Pap) smears.Methods: Women who attended a cancer screening program and who were detected with LSIL were enrolled for the study. Treatment offered was antimicrobials for associated genital infections followed by oral turmeric extract (Curcuma longa Linn, Haldone®, 600 mg, BD) for 10 weeks. The end points for activity were the degree of abnormality in Pap smears and colposcopy, micrometry in Pap smears and serum IL-6 assays, which were carried out initially, at 4-6, and at 10-11 weeks. Safety was assessed clinically, and with blood and urine tests.Results: Out of 21 enrolled cases, 1 discontinued within 2 weeks, and 3 after 4-6 weeks, due to vaginal irritation. Out of 20 cases treated for 4-10 weeks, LSIL did not progress in any case and 18 showed regression in Pap smear scores (p&lt;0.003; Wilcoxan Rank test); 6 showed Cervical Intraepithelial Neoplasia (CIN 1) by colposcopy initially but none post-treatment. No other significant abnormalities were observed clinically, or biochemically. Manual micrometry of Pap smears (N=17) showed a significant reduction in Nuclear diameters &amp; Nucleus/Cytoplasmic ratio (p&lt;0.03; paired t test). A non-significant reduction in serum IL-6 levels occurred in 5/15 cases. Post-therapy Pap smears showed persistent benefit in 16 women after 6-36 months. Conclusions: Non-invasive integrative therapy with antimicrobials followed by standardised oral turmeric extract for 10 weeks appears to be promising for LSIL management by reversing early carcinogenesis through suppression of inflammation and inhibition of NF-kB pathway.

An increase of microRNA-16-1 is associated with the high proliferation of squamous intraepithelial lesions in the presence of the integrated state of HR-HPV in liquid cytology samples.

Studies of cervical cancer (CC) have reported that microRNA-16-1 (miR-16-1), which is an oncomiR, is increased in the tissues and cell lines of CC. The aim of the present study was to investigate the association of miRNA-16-1 expression level with squamous cell carcinoma (SCC), the presence of squamous intraepithelial lesions (SIL) and the integration of high-risk human papillomavirus (HR-HPV) DNA. The current study analyzed 80 samples obtained from women by liquid-based cytology, which revealed that 20 were negative for SIL (NSIL) and without HPV, 20 were low-grade SIL (LSIL), 20 were high-grade SIL (HSIL), and 20 were diagnosed as SCC with HR-HPV. The genotyping of the viral DNA was conducted via an INNO-LiPA-HPV array, the expression of miR-16-1 was determined by reverse transcription-quantitative PCR, and the physical state of the HR-HPV was ascertained by in situ hybridization with amplification with tyramide. A total of eight HR-HPV genotypes were distinguished; the most frequent of these being HPV16, followed by multiple infection with HR-HPV (including HPV16). The mixed state of the HR-HPV was observed in 60 and 65% of LSIL and HSIL cases, respectively, while an integrated HR-HPV state was identified in 90% of cases with SCC. The expression level of miR-16-1 increased according to the grade of SIL, and cases with HSIL exhibited a significantly higher miR-16-1 expression level compared with women with NSIL (P<0.001; Table II). It can therefore be determined that the expression of miR-16-1 effects cellular proliferation, due to the viral integration of various HR-HPV genotypes in unique infection or in multiple infection. Thus, the overexpression of miR-16-1 could be monitored in women with LSIL, in order to discard a major lesion.

What is the Retrospective Correlation between High- Grade Squamous Intraepithelial Lesion (HSIL) on Cytology and the Histological Diagnosis of Cervical Intraepithelial Neoplasia 2 (CIN2) or More in AML, Antwerp, Belgium?

Introduction: Cervical cancer is a major worldwide health problem. Therefore, regular cervical screening in order to make an early diagnosis can help to prevent cervical cancer. The aim of this retrospective study is to evaluate the correlation between HSIL on cytology and histological CIN2+ in AML, Antwerp and to compare two liquid-based cytological techniques ThinPrep® LBC (TP) and SurePath™ LBC (SP). Methods: 120 women with a HSIL positive cytological smear from 2014 (ThinPrep® LBC) and another 120 from 2010 (SurePath™ LBC) were anonymously randomised out of the AML database, according to predefined in- and exclusion criteria. The Belgian Cancer Registry (CIB and CHP) and the AML database were consulted for histological and cytological data and the researched variables (doctor’s speciality, age, HPV status, -genotypes and -persistence) of these 240 women. 184 women, with histological follow-up within one year, out of 240 were included. Statistical analysis was performed using Stata 15.1 (StataCorp, USA). P-values and Odds-ratios were calculated. Results: The CIN2+/HSIL ratio of all included 184 subjects was 75.5% (95%CI=69.3-81.8). The found CIN2+ percentages for TP and SP, were 75.8% (95%CI 67.0-84.6) and 75.3% (95%CI 66.5-84.1) respectively. For all included subjects the variables hrHPV infection (p=0,008; OR=6.97) and HPV16 infection (p=0.004; OR=2.79) were statistically significant for having CIN2+ on histology. Conclusions: The found CIN2+/HSIL ratio of 75.5% in AML, Antwerp is similar to the percentages found in worldwide laboratories. HSIL positive women who are HPV16+ or hrHPV+ are at significant higher risk for invasive cervical disease. No statistically significant difference in CIN2+% was found between the two LBC techniques TP and SP.

Association between Polymorphisms of Glutathione S-Transferase and Progression to Cervical Cancer in Women from Burkina Faso and Mali

Although persistence of high-risk human papillomavirus infection is the main risk factor, Glutathione S-Transferase highly polymorphic enzyme involved in the metabolism of xenobiotics, is a good candidate gene. The objective of this study was to compare the polymorphisms of Glutathione S-Transferase M1-null in women with cancerous lesions and without lesions. This study consisted of 322 uterine cervix samples of women from Mali and Burkina Faso with Cervical Intra-epithelial Neoplasia 2 and 3, adenocarcinoma and squamous cell carcinoma and 100 women with no lesions. Human Papillomavirus genotyping was performed by Real-time multiplex Polymerase Chain Reaction. Glutathione S-Transferase gene polymorphisms were determined using conventional Polymerase Chain Reaction followed by migration on agarose gel. A statistically significant association with high relative risks of 10.77 for the development of High grade Superficial or Squamous Intra-epithelial Lesion (95% CI = 5.59 - 20.72; p < 0.001), and 13.20 for cancer development (95% CI = 6.79 - 25.63; p < 0.001) was found in women with the null genotype of Glutathione S-Transferase M1 in the study population. In Burkina Faso and Mali, Glutathione S-Transferase M1-null presented relative risks of 9 and 11.05 for high-grade lesions, 15 and 11.40 for cancer. Similarly, significant results had been observed in women with human papillomavirus positive and human papillomavirus negative. The results of the present study support the idea that the deletion of Glutathione S-Transferase M1 plays a crucial role in the progression of high-grade lesions and cervical cancer.

Incidence of HPV Negative High Grade Squamous Cell Intraepithelial Lesions in Cervix

Incidence of HPV Negative High Grade Squamous Cell Intraepithelial Lesions in Cervix

Association between viral loads of different oncogenic human papillomavirus types and the degree of cervical lesions in the progression of cervical Cancer

ObjectiveIn this study we determined the frequency of the most prevalent human papillomavirus (HPV) types in China and evaluated the association between viral loads of different oncogenic HPV types and the severity of disease. MethodsWe enrolled 15,518 women for this study and 3199 of them (20.61%) were identified as positive by a PCR assay, that can simultaneously quantify and genotype HPV. ResultsThe viral loads of HPV 16, 31, 35, 52, 58, 39, and 56 were lower for women with normal cytology compared to those with disease progression; viral loads were not appreciable for HPV 33, 18, 45, 59, 68, 53, 66, and 51. The viral load of species 9 appeared significantly higher for women with cervical intraepithelial neoplasia (CIN) 2/CIN 3 relative to women with normal/low grade squamous intraepithelial lesion (LSIL)/CIN1 (P < 0.001), and significantly lower compared to those with cervical cancer (P < 0.001). The viral load of HPV species 6 was slightly higher for women with CIN2/CIN 3 compared to women with normal/LSIL/CIN1 (P = 0.002), and not significantly different from women with cervical cancer (P = 0.548). In addition, no statistically significant difference was found in HPV species 5 or species 7 (P = 0.898; P = 0.136). ConclusionsThe HPV viral load-associated risk for developing into CIN and cervical cancer is likely to be species-dependent and primarily restricted to species 9 (types phylogenetically close to HPV16).

Integración, carga viral y niveles de ARN mensajero de E2 de VPH 16 en la progresión de lesiones intraepiteliales cervicales

Entre las lesiones intraepiteliales escamosas cervicales (LIE) es importante distinguir aquellas asociadas con mayor riesgo de cáncer de cuello uterino. El objetivo de este trabajo fue evaluar si los niveles de expresión de E2 del VPH16 en mujeres con LIE y con evidencia de integración viral se asocian con el grado de la lesión. Se analizaron 109 cepillados cervicales positivos para VPH 16 provenientes de 19 mujeres sin LIE, 45 mujeres con LIE de bajo grado (LIEBG) y 45 mujeres con LIE de alto grado (LIEAG). Se cuantificó el número de copias de ARNm de E2 y de los genes E2 y E6 mediante PCR en tiempo real para determinar la carga viral (E6) y la proporción E2/E6 para evaluar la integración viral. Se encontraron frecuencias similares de expresión de E2 en LEIBG y LEIAG 15/45 (33 %), la frecuencia en mujeres sin lesión fue menor 3/19 (15,8 %), todos los casos en los que se observó expresión del gen E2 tenían mezcla de ADN viral episomal e integrado. La carga viral aumentó significativamente a mayor grado de la lesión (p=0,049), mientras que la proporción E2/E6 disminuyó (p=0,049). El análisis ROC mostró una baja capacidad de los tres parámetros virales para distinguir entre lesiones de bajo y alto grado. En conclusión, aunque las lesiones con presencia de ADN viral mixto e integrado y expresión de E2 podrían estar en menor riesgo de progresión, y la carga viral y la integración se relacionaron con mayor gravedad de la lesión, su valor clínico como biomarcadores de LEIAG es limitado.