Distribution of High-Risk Human Papillomavirus Genotypes among Women with Colposcopic Diagnosis of Cervical Intraepithelial Neoplasia in Bangladesh

Background: The incidence of cervical cancer is high in Bangladesh and there is a high prevalence of preinvasive lower genital tract disease among women of reproductive age. Persistent high-risk Human Papilloma Virus (HPV) infection is the main underlying cause of cervical cancer and its precursor, cervical intraepithelial neoplasia (CIN). Objective: The aim of the study was to identify the subtypes of high-risk HPV infection among women with the colposcopic diagnosis of cervical intraepithelial neoplasia in Bangladesh. Methods: This cross-sectional observational study was conducted in the colposcopy clinic of Dhaka Medical College Hospital over a six-month period. A total of 100 participants were enrolled. Married women, between 30 - 60 years of age with colposcopically diagnosed cervical intra epithelial neoplasia were enrolled. Women with chronic illness, pregnancy, and women unable to consent were excluded from this study. After counselling, colposcopically directed punch biopsies were taken from each CIN case concurrently with high-risk HPV testing by polymerase chain reaction (PCR). Results: The mean age of the patients was 38.69 (SD ±7.76) years. CIN 1 was diagnosed in 57% of participants, while 24% had CIN II and 19% had CIN III lesions. High-risk HPV was present in 52 patients. HPV 16 was the most common identified in 28 (53.84%) and HPV 18 was the second most common with 20 (38.46%) either singly or in combination with other high-risk subtypes. The other HPV strains, HPV 31, 33, 35, 52, 56 and 58, were also detected either as mono or co-infections. Out of the 52 HPV positive cases, 29 (55.8%) had mono infection and 23 (44.2%) had co-infection with several subtypes. The highest incidence (50%) of oncogenic HPV infections was present among women aged 35 - 45 years. Risk factors associated with HPV positive cases were high parity (P 0.05), early age at marriage (P = 0.754) and early age of first child. Conclusion: This study identified a high prevalence of HPV 16 and 18 genotypes. HPV vaccination with the current 9-valent HPV vaccine, which contains HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Will be an effective public health measure to eradicate cervical cancer in Bangladesh.

RELATIONSHIP BETWEEN CYCLIN G1 AND HUMAN PAPILLOMA VIRUS INFECTION IN CERVICAL INTRAEPITHELIAL NEOPLASIA AND CERVICAL CARCINOMA

Objective To evaluate the overexpression of cyclin G1 in cervical intraepithelial neoplasia (CIN) and cervical carcinoma, and the correlation between cyclin G1 and high-risk human papilloma virus (HPV) infection. Methods All of the specimens were obtained from the Department of Pathology of China-Japan Friendship Hospital from January 2000 to August 2004.We detected the expression of cyclin G1 with immunohistochemistry, HPV16/18 infection with in situ hybridization, and high-risk HPV infection with Hybrid capture system II (HC-II) in normal group (25 cases), CIN I (48 cases), CIN II (56 cases), CIN III (54 cases), and invasive cervical squamous-cell carcinoma (SCC, 31 cases). Results The positive rates of cyclin G1 expression in CIN(77.85%)and SCC cervical tissues (87.10%) were significantly higher than normal (8.00%, P<0.01), and the intensities of cyclin G1 expression in CIN(40.60%)and SCC cervical tissues (61.51%) were significantly higher than normal (2.72%, P<0.05). The positive rates and intensities of cyclin G1 expression increased gradually with the grade of cervical lesions. High-risk HPV infection rates were higher in CIN and SCC than normal groups (P<0.05). There was a positive correlation between cyclin G1 expression and high-risk HPV infection detected with HC-II (Kendall’s tau-b=0.316, 0.269, 0.352, and 0.474 in CIN I, CINII, CIN III, and SCC, respectively, P<0.05). Conclusions Cyclin G1 is overexpressed in CIN and SCC. Cyclin G1 may be a biomarker for detecting CIN and SCC. Cyclin G1 may play an important role in the oncogenesis of CIN and SCC by high-risk HPV infection.

Smoking and genital human papilloma virus infection in women attending cervical cancer screening in Greece

AIM: To investigate whether smoking is associated with human papilloma virus(HPV) infection. METHODS: HPV infection is considered to be a neces-sary condition for cervical cancer development. The study population included 1291 women, aged 25-55 years, attending cervical cancer screening. All women had a Papanicolaou(Pap) test, with liquid-based cytology(Thinprep), an HPV-DNA test and an evaluation of smoking habits. The COBAS 4800 system was used for HPV-DNA testing, enabling identifi cation of the following high-risk HPV(hr HPV)-types: each of HPVs 16 and 18 separately, and HPVs 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 as a cocktail. The evaluation of smoking habits was assessed using the smoking intensity index(SII), a variable formed as the product of cigarettes consumed per day by the days(years × 365) that a woman was a smoker, divided by 1000. RESULTS: There were 136 smokers among 238 women tested positive for hr HPV-types(HPVs 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and/or 68), and 463 smokers among 1053 hr HPV-negative women(OR = 1.7, P < 0.001). This association was attributed to the youngest age group of women, aged 25-34 years(OR = 2.3, P < 0.001), while there was no association in other age groups. The intensity of smoking(increasing SII) showed no statistically signifi cant association with hr HPV infection. Cervical infection with HPV 16 and/or HPV 18 was also not associated with age or smoking habits. Finally, no association was found between Pap test status and smoking habits or smoking intensity. CONCLUSION: Smoking appears to be associated with hr HPV infection of the uterine cervix, particularly in younger women. Further studies should investigate whether this association is based on causality and evaluate the role of other possible co-factors.

Correlation between Physical Status of Human Papilloma Virus and Cervical Carcinogenesis

The prevalence of human papilloma virus (HPV)-16 in patients with cervical cancer,the physical status of HPV-16 in patients with cervical lesions,and the role of HPV-16 integration in cervi-cal carcinogenesis were investigated.HPV genotyping was performed by using PCR approach with the primer GP5+/GP6+ and type-specific primer on biopsy specimens taken operatively from 198 women.Multiple PCR was done to detect physical status of HPV-16 in a series of cervical liquid-based cytology samples and biopsy specimens obtained from different cervical lesions with HPV-16 infection,includ-ing 112 specimens with cervical cancer,151 specimens with CINⅠ,246 specimens with CINⅡ and 120 specimens with CINⅢ.The results showed that there were 112 cervical cancer samples (56.57% of total cervical cancer patients) with HPV-16 infection.The frequency of HPV-16 pure integration was 65.18% (73/112),56.57% (47/120),23.58% (58/246) and 7.95% (12/151) in cervical cancer,CINⅢ,CINⅡand CINⅠ patients respectively.In situ hybridization was performed on some paraffin-embedded sections of CINⅡ,CINⅢ and cervical cancer to verify the physical status of HPV-16 infection.Sig-nificant difference was observed between cervical cancer and CINⅠ,CINⅡ,CINⅢ in the frequency of HPV-16 integration (P<0.01).It is suggested that HPV-16 is the most prevalent type and is associated with cervical cancer.In the case of HPV-16 infection there are close associations between the severity of cervical lesions and the frequency of HPV-16 integration.The application of testing HPV genotyping and physical status based on detection of HC-Ⅱ HPV DNA would be in favor of predicting the progno-sis of cervical precancerosis and enhancing the screening accuracy of cervical cancer.

Co-infection of Epstein-Barr virus and human papillomavirus in human tumorigenesis

Viral infections contribute to approximately 12%of cancers worldwide,with the vast majority occurring in developing countries and areas.Two DNA viruses,Epstein-Barr virus(EBV) and human papillomavirus(HPV),are associated with38%of all virus-associated cancers.The probability of one patient infected with these two distinct types of viruses is increasing.Here,we summarize the co-infection of EBV and HPV in human malignancies and address the possible mechanisms for the co-infection of EBV and HPV during tumorigenesis.

Sequence analysis of human papillomavirus type 16 E6E7 gene from cervical carcinoma biopsies of Chinese patients in Shandong province

Objective To study the structure specificity of HPV16E6E7 gene from cervical carcinoma biopsies of patients in Shandong province. Methods The tissue DNAs were extracted from cervical carcinoma biopsies of 14 patients of Chinese from Shandong province. By PCR method using HPV multiple primers, the HPV types were identified in cervical carcinoma tissues, Using the tissue DNA of the 2 cases with the infection of HPV16 type only as templates, HPV16E6E7 gene was amplified by PCR respectively, then inserted the HPV16E6E7 gene into pALTER I vector, and obtained the recombinant plasmid pALTER HPV16E6E7. The constructs were sequenced using Sanger method, and then compared with the sequence of HPV16E6E7 gene of the prototype. Results Sequencing results showed that HPV16E6E7 gene in the 2 cases had sequence diversity from that of the prototype, and a total of five nucleotide exchanges were detected, four of these led to amino acid exchanges. Conclusion There are structure differences between the HPV16E6E7 of Chinese and that of the prototype.

THE CERVIX MULTI－VIRUSES INFECTION AND THE DEVELOPMENT OF CERVICAL CARCINOMAS

The infections of human papilloma virus (HPV),herpes simplex virus type 2 (HSV-2) and Epstein-Barr virus (EBV) to human cervical epithelium are universal and some of them are associated with the development of cervical carcinomas. One hundred and eleven cervical cancer biopsies taken from Beijing area and Xiangyuan county in Shanxi province of China were examined for the presence of DNA sequences of HPV, HSV-2 and EBV by means of Dot blot hybridization. The experiment results showed that the total infectious rates of HPV, HSV-2 and EBV were 71.17% (79/111), 14.44%(16/111) and 15.63% (15/96), respectively. Seventy-nine samples positive for HPV were further analysed for the viral types distribution, the result indicated that the positive specimens of HPV type 16 accounted for 72.15%, otherwise, the biopsies positive for HPV type 18and 6B/11 only accounted for 16-46% and 11.39%,respectively. The data suggested that HPV infection,especially HPV type 16, may play an important role in the development of cervical carcinomas- 16 specimens positive for HSV-2 were examined for HPV DNAsequences and the result uncovered that 13 out of them were HPV16 positive (81.25%), 11 samples containing EBV genomes were also examined for HPV DNA sequences and the result indicated that 9 of 11 were detectable for HPV DNA. The experiment results proved a direct evtidence of multi-virus infection in cervix and of the synergistic interaction among viruses in the process of cervical epithelial carcinogenesis.Comparing of the viruses' infection of two areas, the frequencies of HPV infection in Beijing and Xiangyuan areas were 72.84% (59/ 81) and 66.67% (20/30) , the infectious rates of HSV-2 in the two areas were 8.64%(7/81) and 30% (9/30) (P<0.05), the rates of EBV infection in the two areas were 12.5% (10/80) and 31.25% (5/16)(0.1>P>0.05). The results proved another strong evidence that the high incidence of cervical cancer in Xiangyuan county may be closely correlated with multiviruses infection and with multi-virus synergistic interaction.

Female genital schistosomiasis,human papilloma virus infection,and cervical cancer in rural Madagascar:a cross sectional study

Background Women’s health in resource-limited settings can benefit from the integrated management of high-burden diseases,such as female genital schistosomiasis(FGS)and human papilloma virus(HPV)-related cervical cancer.In schistosomiasis-endemic countries such as Madagascar,data on FGS and HPV prevalence are lacking as well as preventive measures for both conditions.This study aims to estimate the prevalence of FGS and HPV in rural Madagascar,and to examine associated risk factors to identify opportunities for improving women’s health.Methods After initial community outreach activities,interested women aged 18-49 years were recruited consecutively in 2021 at three primary health care centers in the district of Marovoay.FGS was detected by colposcopy.Colposcopy images were double-blind reviewed by two independent specialists.A Luminex bead-based assay was performed on cervical vaginal lavage specimens for HPV typing.Crude(CPR)and adjusted prevalence ratios(APR)of associations between selected factors and FGS and HPV positivity were estimated using univariable and multivariable binary Poisson regression with 95%confidence intervals(CIs).Results Among 500 women enrolled,302 had complete information on FGS and HPV diagnosis,and were thus eligible for analysis.Within the sample,189(62.6%,95%CI:56.9-68.1)cases of FGS were detected.A total of 129 women(42.7%,95%CI:37.1-48.5)tested positive for HPV.In total,80 women(26.5%,95%CI:21.6-31.8)tested positive for both conditions.No association was observed between FGS and HPV positivity,while previous pregnancy(APR=0.65,95%CI:0.43-0.78)and older age(APR=0.59,95%CI:0.42-0.81)are showing a negative association with HPV infection compared to no previous pregnancy and younger age groups.Conclusions The results of the study show that FGS and HPV are highly prevalent in rural Madagascar.The concurrent prevalence of these two conditions requires urgent adaptations of public health strategies to improve women’s health,such as integrated services at primary level of care.

Clinical Observation of rhIL-2 Combined with Zhenqi Fuzheng and BaofuKang Suppository in the Treatment of Cervical Intraepithelial Neoplasia II with HPV Infection

Objective: To investigate the clinical effects of recombinant human interleukin-2 (rhIL-2) combined with Zhenqi Fuzheng and Baofukang on cervical intraepithelial neoplasia II (CINII) combined with human papilloma virus infection. Methods: There were 593 patients diagnosed with CINII with HPV infection, including 296 in the control group and 297 in the experimental group. The control group was given only Zhenqi Fuzheng oral and Baofukang suppository vaginal medicine. The experimental group was treated with rhIL-2 injection in addition to Zhenqi Fuzheng oral and Baofukang suppository vaginal medicine which is treated for 3 months. After 3 months, Thinprep cytologic test (TCT), human papilloma virus (HPV) quantitative examination and colposcopy biopsy were reviewed. Results: After 3 months of treatment, the negative conversion rate and total effective rate of HPV in the control group were 58.11% and 70.95% respectively, and the negative conversion rate and total effective rate of the experimental group were 79.46% and 90.57% respectively. There was significant difference between the two groups (p = 0.000). The curative rate of cervical lesions was significantly higher in the test group than in the control group, 89.56%, 68.91%, respectively. The statistical difference between the two groups is significant (p = 0.000). Conclusion: It has an essential clinical value that HPV infection patients and cervical intraepithelial neoplasia II associated with HPV infection patients are treated by rhIL-2 combined with Zhenqifuzheng and Baofukang, which is safe, effective, non-invasive, reusable advantages. However, the long-term efficacy and side effects need to be further studied.

Correlation analysis of human papillomavirus E6/E7 mRNA detection with diagnosis,prognosis and recurrence risk in patients with cervical epithelioma

BACKGROUND Cervical intraepithelial neoplasia(CIN)is an important precursor of cervical cancer.Early detection and treatment can reduce the incidence of cervical cancer.AIM To investigate the detection rate of human papillomavirus(HPV)E6/E7 mRNA in cervical tissue of patients with different types of epithelial cell neoplasia(CIN)and its relationship with CIN progression and diagnosis.METHODS One hundred women with HPV infection detected by cervical exfoliation cytology between January 2022 and January 2023 were retrospectively selected.These patients were graded CIN based on colposcopy and cervical pathology.The positive expression rates of HPV E6/E7 mRNA and HPV[polymerase chain reaction(PCR)-reverse dot crossing]were compared among all groups.Patients with HPV E6/E7 mRNA expression in the grade 1 CIN group were followed up for 1 yr.The relationship between atypical squamous epithelium and high malignant epithelial neoplasia was investigated by univariate and multivariate analysis.RESULTS The diagnostic sensitivity,specificity,and sensitivity of PCR-reverse point hybrid ization technology for secondary CIN were 70.41%,70.66%,and 0.714,respectively.Sensitivity and specificity for secondary CIN were 752%and 7853%,respectively,the area under the curve value was 0.789.Logistic Multifactorial model analysis revealed that the HPV positive rates and the HPV E6/E7 mRNA positive rates were independent risk factors of CIN grade I(P<0.05).In CIN grade I patients with positive for HPV E6/E7 mRNA,in its orientation to grade CIN patients,in its orientation to grade CIN patients,at 69.2%,compared with patients negative for HPV E6/E7 mRNA(30.8%),significant difference(P<0.05).CONCLUSION HPV E6/E7 mRNA and HPV(PCR-reverse dot hybrid)positive expression have a close relationship with CINgrade disease progression and is an independent risk factor for high-grade CIN lesions.

THE INFECTION OF EBV FOR CERVICAL EPITHELIUM-A NEW CAUSITIVE AGENT IN THE DEVELOPMENT OF CERVICAL CARCINOMAS?

Epstein-Barr virus was considered as a caustive agent for Burrkitt' s lymphoma and non-malignant B lymphocytes proliferation. The recent studies revealed the striking association of the Infection of EBV with the development of human epithelial tumors. 43 specimens of normal exfoliated cervical epithelial cells, 47 biopsies of chronic cervlcitis and 80 tissue samples of cervical carcinomas were tested for the presences of EBV W fragments by using dot blot hybridization method. The results showed that the detectable rates of EBV DNA sequences In the normal exfoliated epithelium, the chronic cervlcitis and cervical carcinomas were 44.16%, 12.77% and 13.75%, respectively. Eleven EBV positive DNA samples from cervical cancers were also examined for the presence of HPV DNA. The result showed 9 out of 11 were HPV DNA positive, the cultanious infectious rate of both viruses was about 81.81%.In this paper, the EBV genomes existed In the part of biopsies of cervical carcinomas were first reported. The results Implied that the development of cervical cancer might be associated with asymptomatic EBV Infection In early stage and might be the result from the synergistic carcinogenesis of EBV with other cervical oncovinises, especially with HPV.

Studies on the correlation between human papilloma virus vaccine and premature ovarian failure

Cervical cancer is the most common malignant tumour of the female reproductive system,resulting in more than 500,000 new cases annually worldwide.In developing countries,cervical cancer ranks second in terms of cancer mortality among women.Human papilloma virus is the primary causative agent of cervical cancer,with approximately 70 percent of cervical cancers caused by high-risk types of human papilloma virus 16 and 18.There are currently three types of human papilloma virus vaccines available:bivalent,quadri-valent and nine-valent.However,in recent years,it is reported that cervical cancer vaccine can cause premature ovarian failure.Consequently,an extensive literature search to find out the correlation between human papilloma virus vaccine and premature ovarian failure became a priority.There is no sufficient evidence to support or prove that there is a link between the human papilloma virus vaccine and premature ovarian failure.Hence,the vaccine does not cause premature ovarian failure.

DNA methyltransferase (DNMTs) expression in cervical cancer tissues and its relationship with HPV infection and tumor malignancy

Objective:To study the DNA methyltransferase (DNMTs) expression in cervical cancer tissues and its relationship with human papilloma virus (HPV) infection and tumor malignancy. Methods:The cervical cancer tissues and normal cervical tissues surgically removed in Department of Obstetrics and Gynecology of our hospital between July 2013 and March 2016 were collected, the fluorescent quantitative PCR method was used to determine the mRNA expression of DNMTs in the tissues, and enzyme-linked immunosorbent assay kits were used to determine the protein expression of DNMTs molecules and pro-apoptotic molecules in the tissues. Results:DNMT1, DNMT2, DNMT3a, DNMT3b and DNMT3l mRNA expression and protein expression in cervical cancer tissues were significantly higher than those in normal cervical tissues (P<0.05) while Fas, FasL, Bax and Caspase-3 protein expression were significantly lower than those in normal cervical tissues (P<0.05);DNMT1, DNMT2, DNMT3a, DNMT3b and DNMT3l protein expression in cervical cancer tissues with high-risk HPV infection (+) were significantly higher than those in cervical cancer tissues with high-risk HPV infection (-) (P<0.05);Fas, FasL, Bax and Caspase-3 protein expression were negatively correlated with DNMT1, DNMT2, DNMT3a, DNMT3b and DNMT3l protein expression. Conclusions:Elevated DNMTs expression in cervical cancer tissues is associated with high-risk HPV infection, and highly expressed DNMTs can inhibit the expression of pro-apoptotic molecules.

Revisiting HPV infection pattern among urban Indonesian women in general population and its implication on health burden:A cross-sectional analysis from Indonesian Noncommunicable Disease Research 2016

Objective:To identify circulating HPV types among urban Indonesian women and their specific co-infection patterns in bid to curb HPV infection in the general population and minimize its complications.Methods:Urban Indonesian women from general population were selected as sample framework.Sample size and distribution across regions were determined by the Indonesian Bureau of Statistics(Badan Pusat Statistik,BPS),which represented the national level.Up to 35408 cervical swab specimens were collected from August to September 2016 in 34 Indonesian provinces,categorized into six regions based on the development criteria set by the Ministry of National Development Planning(Badan Perencanaan Pembangunan Nasional,BAPPENAS).From all 1874 samples identified as HPV-positive,hybrid capture was implemented to evaluate type-specific HPV.This study analyzed descriptive data to determine the core-cluster of HPV combination.Co-occurrence HPV network was assessed using‘qgraph’package version 1.6.3 and computed in R version 3.6.3.Two-HPV association was analyzed in logistic regression using bias-reduction generalized linear model(brglm2)package version 0.5.1 adjusted by age and six main Indonesian regions.Results:The logistic regression analysis demonstrated that HPV type 52 had rare relationship despite its common co-occurrence,cementing its role in single HPV infection.HPV type 16 and 18 tended to form infection cluster and were strongly associated with other types.Conclusions:HPV type 52 was the most frequent HPV type among urban Indonesian women and accounted for most single infection cases.Concurrently,HPV 16 and HPV 18 accounted for most multiple infection cases and had strong tendency to attract other types,which may add further complications.However,due to lack of cytology and histological examination and information for other potential determinants,further in-depth studies are necessary to confirm whether these infection patterns truly connect to certain clinical outcomes.

Clinical significance of human papilloma virus infection in the cervical lesions

Cervical lesions have been regarded as the common and frequently occurring diseases in China.Recently,the morbidity and youth tendency of cervical cancer have gradually increased.Cervical cancer,related with human papilloma virus(HPV)infection,has been one of the severest diseases threatening health and life of women,and is an infectious disease.The universality of HPV infection in the reproductive tract should not be ignored.The well-known risk factors of HPV infection in cervical lesions consist of high-risk sexual behaviors,immunosuppression,age,contraceptive methods,the concurrent infection of other sexually transmitted diseases,etc.The variation of cervical lesions induced by HPV infection is involved in the continuous pathological process,including the subclinical,latent,and persistent infection of high risk(HR)-HPV,chronic cervicitis with abnormal results of cytological examination,cervical intraepithelial neoplasia(CIN),and cervical cancer.The outcome of patients with HPV infection is influenced by many factors,such as HPV subtype dominance,persistent HPV infection,HPV loading dose,and multiple HPV infection.Controlling HR-HPV persistent infection should be an important strategy for reducing cervical lesions.

Cervical cancer: Can it be prevented?

Cervical cancer prevention requires a multipronged approach involving primary, secondary and tertiary prevention. The key element under primary prevention is human papilloma virus(HPV) vaccination. So far, only prophylactic HPV vaccines which prevent HPV infection by one or more subtypes are commercially available. Therapeutic HPV vaccines which aid in clearing established infection are still under trial. Secondary prevention entails early detection of precancerous lesions and its success is determined by the population coverage and the efficacy of the screening technique. A number of techniques are in use, including cytology, visual inspection(using the naked eye, magnivisualizer, acetic acid and Lugol's iodine), HPV testing and a combination of these methods. Updated screening guidelines have been advocated by the American Cancer Society in light of the role of HPV on cervical carcinogenesis. Recent research has also focussed on novel biomarkers that can predict progression to cancer in screen positive women and help to differentiate those who need treatment from those who can be left for follow-up. Last but not the least, effective treatment of precancerous lesions can help to reduce the incidence of invasive cervical cancer and this constitutes tertiary prevention.A combination of these approaches can help to prevent the burden of cervical cancer and its antecedent morbidity and mortality, but all of these are not feasible in all settings due to resource and allocation constraints. Thus, all countries, especially low and middle income ones, have to determine their own cocktail of approaches that work before we can say with certainty that yes, cervical cancer can be prevented.

Sanguinarine-Mediated Sensitization of Cervical Cancer SiHa Cells to TRAIL

Introduction: Cervical cancer is primarily caused by the human papilloma virus (HPV), which transforms normal cervical cells into cancerous cells that are highly resistant to radiation and chemotherapy. Induction of apoptosis in transformed cells is a key strategy in successfully treating HPV-induced cervical cancer. TRAIL (tumor necrosis factor related apoptosis-inducing ligand) has been shown to selectively induce apoptosis in cancer cells by binding to death receptors and activating extrinsic pathways for apoptosis. However, certain cervical cancers—such as the cultured cell line SiHa—are remarkably resistant to TRAIL. In this study, SiHa cells were sensitized to TRAIL by using sanguinarine—derived from the plant Sanguinaria Canadensis—which is known to induce oxidative stress and lead to the upregulation of receptors for TRAIL. Methods: Cultured SiHa cells were exposed to sub-lethal doses of sanguinarine in combination with TRAIL. Cell viability changes as well as the production of reactive oxygen species (ROS) were assessed. The induction of apoptosis was investigated by assays for caspase activation. Flow cytometry was performed to analyze expression of death receptors 4/5. Results: Treatment of SiHa cells with a combination of sanguinarine and TRAIL led to a significant reduction in cell viability. Significant increase in ROS was observed and caspase activation assays confirmed the induction of apoptosis. Conclusions: The observed synergistic effect of sanguinarine and TRAIL on SiHa cells is promising for the treatment of cervical, and possibly other, HPV-induced cancers. Oxidative stress caused by sanguinarine seems to play a central role in this synergy. The precise link between reactive oxygen species and the possible upregulation of death receptors needs further investigation. This knowledge will enable us to devise more effective treatments for those who suffer from this devastating disease.

保妇康栓联合臭氧治疗宫颈高危型人乳头瘤病毒感染的应用效果

目的观察宫颈高危型人乳头瘤病毒(HR-HPV)感染采用保妇康栓联合臭氧治疗的应用效果。方法选取2018年3月至2020年12月在南昌大学第四附属医院妇科检查中HPV检测为阳性的120例患者作为研究对象,根据随机数字表法分为试验组(60例)和对照组(60例)。对照组采用保妇康栓治疗,试验组采用保妇康栓联合臭氧治疗,两组共治疗3个疗程。比较两组患者的临床疗效、HPV转阴率、血清肿瘤坏死因子α(TNF-α)水平,白细胞介素-6(IL-6)水平、转化生长因子-β(TGF-β)水平和不良反应总发生率。结果试验组治疗总有效率高于对照组,差异有统计学意义(P<0.05);试验组HR-HPV转阴率高于对照组,差异有统计学意义(P<0.05);试验组治疗后TNF-α、TGF-β水平低于对照组,IL-6水平高于对照组,差异有统计学意义(P<0.05);两组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论对宫颈HR-HPV患者采用保妇康栓联合臭氧治疗,效果确切,能够提高HPV转阴率,且安全性较高,值得临床推广应用。

人乳头瘤病毒DNA、E6/E7 mRNA及液基薄层细胞学检查对女性宫颈癌的筛查价值

目的探讨人乳头瘤病毒(HPV)DNA、E6/E7 mRNA及液基薄层细胞学检查(TCT)对女性宫颈癌的筛查价值。方法选取28021例体检女性,均接受HPV DNA、E6/E7 mRNA和TCT单项或多项检测,记录HPV DNA、E6/E7 mRNA、TCT单独及联合检测对宫颈癌的检出情况。以组织活检结果为金标准,评估HPV DNA、E6/E7 mRNA、TCT单独或联合检测对宫颈癌的筛查价值。结果TCT、HPV DNA、E6/E7 mRNA对宫颈癌的检出率分别为8.8%、26.9%、29.7%。各方法单独检测时,TCT单独检测筛查宫颈癌的特异度最高(85.53%),但灵敏度最低(28.44%),HPV DNA单独检测筛查宫颈癌的灵敏度最高(60.25%)。两种方法联合检测时,HPV DNA+E6/E7 mRNA联合检测筛查宫颈癌的灵敏度最高(81.75%),特异度最低(26.34%),TCT+HPV DNA联合检测筛查宫颈癌的特异度(61.08%)和阴性预测值(57.11%)最高,任意两种方法联合检测筛查宫颈癌的灵敏度、特异度比较,差异均有统计学意义(P﹤0.05)。TCT+HPV DNA+E6/E7 mRNA联合检测筛查宫颈癌的灵敏度、特异度与HPV DNA+E6/E7 mRNA检测比较,差异均无统计学意义(P﹥0.05),但灵敏度高于TCT+E6/E7 mRNA联合检测,特异度低于TCT+E6/E7 mRNA联合检测,差异均有统计学意义(P﹤0.05)。结论HPV DNA检测适合作为女性健康体检者宫颈癌筛查的首选方法,E6/E7 mRNA与TCT检测可作为宫颈癌进一步检查的优选。HPV DNA+E6/E7 mRNA联合检测具有较高的灵敏度和阳性预测值,可作为年轻女性宫颈癌筛查的优选方案,联合检测对提高阳性率及降低假阳性率有帮助。

山东省滕州地区女性HPV亚型分布特点及其与女性宫颈病变的关系

目的 对山东省滕州地区女性人乳头瘤病毒(HPV)亚型分布特点及其与女性宫颈病变的关系进行分析和探讨。方法 选取2023年1月至2023年10月于我院行HPV检查的20 378例女性为研究对象,收集其HPV检查结果、薄层液基细胞学检查检查结果以及宫颈组织活检结果,探讨HPV亚型分布特点及其与女性宫颈病变的关系。结果 20 378例受检者中,HPV阳性率34.81%,其中,高危型感染5989例(84.42%),低危型感染2095例(29.53%)。宫颈病变率39.34%,其中,HPV高危型感染患者占比高于HPV低危型感染患者(P <0.05),且HPV 16型感染率随着病变程度的加深显著提高(P <0.05)。不同宫颈病变患者中,多重感染与单一感染率占比相当(P> 0.05)。结论 在宫颈病变患者中,最常见的HPV基因亚型为HPV 52、58、16、18,其中,HPV 16的检出率与病变程度之间存在正相关关系。多重感染不会对宫颈病变程度产生显著影响。在临床实践中,必须高度重视高危HPV 16、52、58亚型患者的阴道镜分流管理。