T helper cell and regulatory T-cell related cytokines changes in vaginal lavage fluid of patients with high risk-human papilloma virus 16 positive and the predictive effect on the development of cervical neoplasms / 肿瘤研究与临床

Objective:To investigate the changes of T helper cell (Th), regulatory T-cell (Treg cell) related cytokines in vaginal lavage fluid of patients with high risk-human papilloma virus 16 (HR-HPV16) positive and its predictive effect on the development of cervical neoplasms.Methods:A total of 200 cases of HR-HPV16 positive patients who admitted to Xingtai People's Hospital from January 2022 to December 2022 were selected as the experimental group. According to the results of pathological examination, all patients in the experimental group were divided into non pathological group (78 cases), low grade squamous intraepithelial lesion (LSIL) group (49 cases), high grade squamous intraepithelial lesion (HSIL) group (39 cases) and cervical cancer group (34 cases); and 100 healthy people undergoing the physical examination in the same period were taken as the healthy control group. Enzyme-linked immunosorbent assay (ELISA) double-antibody sandwich method was used to detect the levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) and transforming growth factor β (TGF-β) in vaginal lavage fluid of patients in different groups. Multivariate logistics regression was used to analyze the risk factors of cervical cancer, and a nomogram model was established. The receiver operating characteristics (ROC) curve was drawn with pathological results as the gold standard, and the area under the curve (AUC) was calculated to evaluate the predictive ability of the nomogram model.Results:The levels of IL-6, IL-10, IL-17, TNF-α, TGF-β in vaginal lavage fluid of patients in the experimental group were higher than those in the healthy control group, while the levels of IL-2, IL-12 and IFN-γ in the experimental group were lower than those in the healthy control group, and the differences were statistically significant (all P < 0.05); the difference in IL-4 level of both groups was not statistically significant ( P > 0.05). There were statistically significant differences in IL-6, IL-10, IL-17, TNF-α, TGF-β, IL-2, IL-12 and IFN-γ among non pathological group, LSIL group, HSIL group and cervical cancer group (all P < 0.05); the levels of IL-6, IL-10, IL-17, TNF-α, TGF-β in cervical cancer group were the highest, the levels of IL-2, IL-12 and IFN-γ were the lowest; the level of IL-4 in non pathological group, LSIL group, HSIL group and cervical cancer group had no statistically significant difference ( P > 0.05). Logistics regression analysis showed that low IL-2, high IL-4, high IL-6, high IL-10, low IL-12, high IL-17, high TNF-α, low IFN- γ and low TGF-β expressions in vaginal lavage fluid of patients with HR-HPV16 positive were independent risk factors for the development of cervical cancer (all P < 0.05). The results of nomogram analysis showed that IL-6, IL-10, IL-17, TNF-α, TGF-β in vaginal lavage fluid were the factors predicting the development of cervical cancer in HR-HPV16 positive patients. The ROC curve analysis showed that the AUC of nomogram model in predicting the development of cervical cancer in HR-HPV16 positive patients was 0.945 (95% CI 0.901-0.988), and the predictive efficacy was good. Conclusions:Th and Treg cell related cytokines levels in vaginal lavage fluid of patients with HR-HPV16 positive show pathological changes in cervical cancer patients and the above indicators have a high value in predicting the development of cervical cancer.

Expression of IL-17 and estrogen and its receptor in HPV16 continuously infected patients / 局解手术学杂志

Objective To understand the role of estrogen,estrogen receptor and IL-17 in human papillomavirus (HPV) infection and clearance.Methods We selected the clinic or the hospitalized patients in People' s Hospital of Pudong New District hospital with HPV negative or single-HPV16 positive during the period of August 2014 to January 2017.Cervical exfoliated cells were harvested by Thinprep cytologic test (TCT).The reverse spot hybridization technique was carried out for HPV subtype analysis.RT-PCR was employed for HPV16 DNA viral load.The levels of E2 and IL-17 were detected by ELISA.Immunohistochemical was used to detect ER expression.The experiments were repeated every three months.According to the difference in the outcome of human papilloma virus 16 infection,the experiment was divided into three groups.The first group was HPV negative,which was negative for one year.The second group was HPV16 positive,but within one year the difference was gradually cleared.The third group was HPV16 positive,but the HPV16 persistently existed after one year.Results The results of the last test were compared with the first test results.We found that There was no significant difference among the three groups in the expression of E2 and ER.Also,there was no significant difference between the HPV negative group and the HPV16 persistently infected group in variation of IL-17 concentration.But the difference between the HPV16 cleared group and the anyone of the two groups above was significantly.The variation of IL-17 concentration was significantly higher in the HPV16 cleared group.Conclusion In normal cytology,and only HPV16 infected stage,endogenous E2 and ER of cervix may not play a role in HPV infection,or they may have little effect on HPV infection.Local immune factor IL-17 plays an important role in the process of HPV16 removal,and the increase of IL-17 concentration can help to eliminate HPV16.

Correlation between Severity of Cervical Lesions and Methylation of Human Papilloma Virus Type 16 DNA / 中国医科大学学报

Objective To quantifiably measure the methylation frequency of 18 CpG sites in the 3′region of L1 gene and long control region(LCR) gene of HPVl6 DNA,and study the relationship between HPVl6 DNA methylation and severity of cervical lesions. Methods A total of 10 cases Normal/low?grade squamous intraepithelial lesion(Normal/LSIL),10 cases of high?grade squamous intraepithelial lesion(HSIL),and 10 cases of cervical cancer(CC)were recruited for the study. The relationship between severity of cervical lesions and HPV16 DNA methylation was analyzed by bisultlte?pyrosequencing. Results The methylation rate was highest in Normal/LSIL at position 7 089 located in 3′?L1,followed by CC. The low?est was found in HSIL. The difference in methylation percentage among the three lesions was significant(P=0.006). In 7 134,the proportion meth?ylation was also different among three groups(P=0.01),difference in methylation percentage between Normal/LSIL and CC,as well as Normal/LSIL and HSIL was significant(P=0.038,0.017). Conclusion The methylation status of CpG sites 7 089 and 7 134 in the 3′region of L1gene is asso?ciated with the severity of cervical disease. The quantification of HPV DNA methylation can be used for cervical disease screening in clinical samples.

RESEARCH THE EXPRESSION OF HIGH RISK HUMAN PAPILLOMA VIRUS AND P16 PROTEIN IN CERVICAL INTRAEPITHELIAL LESION BY IMMUNOHISTOCHEMISTRY CH ABOUT LAPAROSCOPY ASSISTED VAGINAL HYSTERECTOMY / Шинэ санаа Шинэ нээлт

The persistent high-risk human papilloma virus(HPV) infection is a necessary cause for developing cervical carcinoma. Although carcinogenic HPV types are found in virtually all invasive cancer, with types 16 and 18 being found in approximately 70 percent of cases. High risk HPV types’ Е6 and Е7 oncogenes have a pivotal role in cervical carcinogenesis. The p16, the cyclin-dependent kinase inhibitor and p16 overexpression in cervical neoplasia is a surrogate marker of high risk HPV E7 mediated pRb catabolism reflecting disruption of mechanisms that control cell proliferation and indicating persistent infection with high risk of development of neoplasia.Thus in worldwide p16 had been identified as the novel biomarker in pre-invasive cervical lesions. Objective: For the purpose to detect for cervical cancer risks we examined HPV16/18 and cell cycle protein p16 expression in cervical lesions.A total of 96 specimens enrolled in this study and 50 were diagnosed as LSIL and 46 were diagnosed as a HSIL. To detect HPV16/18 and p16 in cervical lesions used immunohistochemistry. Statistical analysis was performed using SPSS 16.0. Descriptive analysis was performed by Chi- Square test and also determined sensitivity and specificity.Positive stainingfor p16 and HPV16/18 were observed whole cell, within both the nuclear and cytoplasmic subcellular regions by immunohistochemistry. 63% of specimens had only HPV16 infection and 22% of specimens had only HPV18 infection.Also 14% specimens had co-infection with two viral types and 28% specimens had not above two most HPV infection. There were a significant difference for HPV16 positivity (X2 = 4.93, P 0.05) in HSIL and LSIL groups. There were not a difference for p16 in HSIL and LSIL groups.(X2 = 0.23, P > 0.05), respectively.P16, yielding a diagnostic sensitivity for HPV 16/18 were 82% and 30%, specificity for HPV 16/18 were 40% and 80%, respectively. In conclusion it is possible to detect high risk HPV types and persistent infection by immunohistochemistry in cervical intraepithelial squamous cell lesions. There is still critical need to use HPV testing and other molecular surrogate markers of HPV such as p16 in primary screening program.

Not Just for Tobacco Users Anymore!!! The Emerging Evidence of Human Papilloma Virus: An Overview.

Head and neck squamous cell carcinoma (HNSCC) have a broad and varying rate of incidence and mortality around the world. Tobacco smoking and chewing, alcohol consumption are the main etiological agents for HNSCC and have been estimated to account for the majority of disease burden worldwide. Over the past 20 years, there has been an increasing awareness about the human papilloma virus (HPV), the necessary cause of cancer of the cervix that has been etiologically linked with oropharyngeal cancer. Often diagnosed at a late stage this subset of squamous cell carcinoma of the head and neck has an affi nity for the oropharynx and tends to show low diff erentiation histopathologically and better prognosis regardless of the treatment strategy. Th e HPV belongs to the papillomavaviridiae group of virus which can infect the mucosal and cutaneous epithelia in a species-specifi c manner inducing cellular proliferation. Th e HPV can cause active subclinical infection without clinical signs or can also cause clinical infection that can lead to benign, potentially malignant or malignant lesions. Hence, this overview attempts to focus on the relevant characteristics of HPV and its role in oropharyngeal cancer.

Significance of detection of suPAR, SCC-Ag and HPV16, 18 in patients with cervical cancer / 肿瘤研究与临床

Objective To evaluate the significance of suPAR,SCC-Ag in plasma and HPV16,18 in cervical secretion for monitoring pathogenetic condition and prognosis in patients with cervical cancer.Methods 206 cervical cancer patients blood and cervical secretion were collected.Plasma level of suPAR and SCC-Ag were measured by enzyme linked immunosorbent assay (ELISA) in health women and patients with cervical cancer.The expression of HPV16,18 of cervical secretion in control group and patients with cervical cancer were detected by fluorescence quantitative PCR.The correlations of the three indexes were analyzed.Results The plasma level of suPAR and SCC-Ag,the expression of HPV16,18 of cervical secretion in cervical cancer patients were obviously higher than those in health controls with statistical significance ((1.072 5±0.305 2) ng/ml vs (0.501 7±0.179 3) ng/ml,(0.980 6±0.162 7) μg/ml vs (0.261 4± 0.006 3) μg/ml and 53.89 ％ (90/167),46.15 ％ (18/39) vs 6.67 ％ (4/60),P ＜ 0.05).There was a positive correlation between plasma suPAR level and SCC-Ag level in invasive carcinoma of cervix patients (r =0.564,P ＜ 0.05).The plasma level of suPAR between in HPV16,18 positive group and in HPV16,18 negative group did not show difference (P ＞ 0.05).Conclusions In invasive carcinoma of cervix patients,there is a positive correlation between plasma suPAR level and SCC-Ag level.But it's not yet to conclude that plasma suPAR level of cervix invasive carcinoma patients is related to infection of HPV16,18.

¿Es el momento de vacunar contra el Virus del Papiloma Humano en Colombia? / Is it time to vaccinate against human papilloma virus in Colombia?

Objetivo: analizar el estado actual de la evidencia de la vacunación para el virus de papiloma humano (VPH) a nivel poblacional teniendo como referente su posible aplicación en Colombia. Metodología: evaluación de estudios fase III sobre las vacunas contra el VPH: estudios de los grupos FUTURE I, II y PATRICIA. Se reflexiona sobre su generalización a nivel poblacional y se analizan factores que limitan su uso. Resultados: la evaluación de estos estudios encuentra limitaciones metodológicas que controvierten la eficacia presentada en las publicaciones de los estudios como son la elección de variables sustitutas inadecuadas, análisis de resultados con variables primarias compuestas que son heterogéneas, análisis por protocolo y no por intención de tratamiento, criterios de inclusión que no sustentan la aplicación poblacional de la vacuna en menores de 15 años y factores que pueden afectar la validez de los estudios como conflictos de intereses y origen del patrocinio. De otra parte, se presentan reportes de complicaciones con la aplicación de la vacuna que brindan una mejor información sobre el verdadero comportamiento de este método de prevención por fuera del diseño experimental. Conclusiones: para el momento de esta revisión no se tiene la suficiente evidencia que sustente la inclusión de la vacuna contra el VPH como programa de vacunación poblacional en Colombia

Objective: analysing current evidence regarding proposals for vaccinating the Colombian population against human papilloma virus (HPV). Methodology: assessing HPV vaccine phase III studies (FUTURE I, II and PATRICIA study groups). Comments are made regarding generalising such vaccination amongst the general population, also taking factors limiting their use into consideration. Results: methodological limitations were found when assessing these studies thereby challenging the importance of the efficacy found in such studies such as the choice of inadequate substitutes, analysing results involving heterogeneous primary compounds, analysis by protocol and not by intention to treat, inclusion criteria which did not underpin a general vaccination programme for girls aged younger than 15 and factors which could affect the validity of the studies such as conflicts of interests and sources of sponsorship. Several complications have been reported regarding how the vaccine has been applied, providing better information about this prevention method’s real behaviour (i.e. when taken beyond its experimental design stage). Conclusions: there was not sufficient evidence to recommend introducing HPV vaccination within Colombian immunisation schedules when this review was made

Induction of SiHa Cells Cells Apoptosis by Nanometer Realgar Suspension and Its Mechanism / 华中科技大学学报（医学）（英德文版）

The effects of nanometer realgar suspension on proliferation and apoptosis of human uterine cervix cancer cell line SiHa cells and oncogenic genes HPV16E6/E7 were investigated. A "micro-jet efflux" strategy was used for the preparation of nanometer realgar suspension. SiHa cells were treated with nanometer Realgar suspension in various concentrations (6.25,12.5,25 and 50mg/L) for different durations (12,24,48 and 72h). The inhibitive effect of nanometer realgar suspension on growth of SiHa cells was detected by MIT method. Special morphological changes of apoptosis were observed by transmission electron microscopy (TEM) and DNA fragments electrophoresis. The apoptotic rate was quantified by flow cytometry (FCM). The expression of HPV16E6/E7 mRNA and protein was assayed by RT-PCR and Western blot respectively. The results showed after being treated with 25-50mg/L nanometer realgar suspension for 48h, the survival rate of SiHa cells was decreased, and apoptotic rate markedly increased in a time- and concentration-dependent manner. TEM and DNA electrophoresis revealed the special morphological changes of apoptosis. The apoptotic rate of SiHa cells treated with nanometer realgar suspension was significantly higher than in the control group (P<0.01), and G0/G1 phase arrest appeared following treatment with nanometer realgar suspension in 25 and 50mg/L for 48h.RT-PCR and Western blot assay indicated that nanometer realgar suspension reduced the HPV16E6/E7 gene expression. Nanometer realgar suspension could inhibit the proliferation and induce apoptosis of SiHa cells. The mechanism may be related to the down-regulation of the HPV16E6/E7 gene expression.