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.

Incidence of human papilloma virus in esophageal squamous cell carcinoma in patients from the Lublin region

AIM:To assess the prevalence of human papilloma virus(HPV) in esophageal squamous cell carcinoma(ESCC) in the south-eastern region of Poland.METHODS:The study population consisted of 56 ESCC patients and 35 controls.The controls were patients referred to our department due to other nonesophageal and non-oncological disorders with no gross or microscopic esophageal pathology as confirmed by endoscopy and histopathology.In the ESCC patients,samples were taken from normal mucosa(56 mucosa samples) and from the tumor(56 tumor samples).Tissue samples from the controls were taken from normal mucosa of the middle esophagus(35 control samples).Quantitative determination of DNA was carried out using a spectrophotometric method.Genomic DNA was isolated using the QIAamp DNA Midi Kit.HPV infection was identified following PCR amplification of the HPV gene sequence,using primers MY09 and MY11 complementary to the genome sequence of at least 33 types of HPV.The sequencing results were computationally analyzed using the basic local alignment search tool database.RESULTS:In tumor samples,HPV DNA was identified in 28 of 56 patients(50%).High risk HPV phenotypes(16 or/and 18) were found in 5 of 56 patients(8.9%),low risk in 19 of 56 patients(33.9%) and other types of HPV(37,81,97,CP6108) in 4 of 56 patients(7.1%).In mucosa samples,HPV DNA was isolated in 21 of 56 patients(37.5%).High risk HPV DNA was confirmed in 3 of 56 patients(5.3%),low risk HPV DNA in 12 of 56 patients(21.4%),and other types of HPV in 6 of 56 patients(10.7%).In control samples,HPV DNA was identified in 4 of 35 patients(11.4%) with no high risk HPV.The occurrence of HPV in ESCC patients was significantly higher than in the controls [28 of 56(50%) vs 4 of 35(11.4%),P < 0.001].In esophageal cancer patients,both in tumor and mucosa samples,the predominant HPV phenotypes were low risk HPV,isolated 4 times more frequently than high risk phenotypes [19 of 56(33.9%) vs 5 of 56(8.9%),P < 0.001].A higher prevalence of HPV was identified in female patients(71.4% vs 46.9%).Accordingly,the high risk phenotypes were isolated more frequently in female patients and this difference reached statistical significance [3 of 7(42.9%) vs 2 of 49(4.1%),P < 0.05].Of the pathological characteristics,only an infiltrative pattern of macroscopic tumor type significantly correlated with the presence of HPV DNA in ESCC samples [20 of 27(74.1%) vs 8 of 29(27.6%) for ulcerative or protruding macroscopic type,P < 0.05].The occurrence of total HPV DNA and both HPV high or low risk phenotypes did not significantly differ with regard to particular grades of cellular differentiation,phases in depth of tumor infiltration,grades of nodal involvement and stages of tumor progression.CONCLUSION:Low risk HPV phenotypes could be one of the co-activators or/and co-carcinogens in complex,progressive,multifactorial and multistep esophageal carcinogenesis.

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, CIN Ⅱ, 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.

Human papilloma virus and esophageal carcinoma in a Latin-American region

AIM:To investigate the presence of high-risk human papilloma virus (HPV) in esophageal squamous cell carcinomas (ESCCs) in a non-selected Mexican population.METHODS: Cases with a pathological diagnosis of squamous cell carcinoma of the esophagus were obtained from Department of Pathology files, at the National Cancer Institute in Mexico City during the period between 2000 and 2008. Slides from each case were reviewed and cases with sufficient neoplastic tissue were selected for molecular analysis. DNA was extracted from paraffin-embedded tissue samples for polymerase chain reaction analysis to detect HPV DNA sequences. Demographic and clinical data of each patient were retrieved from corresponding clinical records.RESULTS: HPV was detected in 15 (25%) of ESCCs. HPV-16 was the most frequently observed genotype, followed by HPV-18; HPV-59 was also detected in one case. Unfortunately, HPV genotype could not be established in three cases due to lack of material for direct sequencing, although universal primers detected the presence of HPV generic sequences. No low-risk HPV genotypes were found nor was HPV-16/18 co-infection. HPV presence in ESCC was not significantly associated with gender, age, alcohol consumption, smoking, anatomic location, or histologic grade. All patients belonged to low and very low socioeconomic strata, and were diagnosed at advanced disease stage. Male patients were most commonly affected and the male:female ratio in HPV-positive ESCC increased two- fold in comparison with HPV-negative cases (6.5:1 vs 3.1:1).CONCLUSION: High prevalence of high-risk HPV in ESCC in Mexico does not support the hypothesis that HPV-associated ESCC is more common in areas with higher ESCC incidence rates.

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.

Potential role of human papilloma virus in the pathogenesis of gastric cancer

AIM: To demonstrate the presence and biological activity of human papilloma virus (HPV) in gastric cancer (GAC) tissues.

Human papilloma virus 16 E6 oncoprotein associated with p53 inactivation in colorectal cancer

AIM:To investigate the association between human papilloma virus(HPV) infection and colorectal cancer.METHODS:Sixty-nine patients with pathologically confirmed primary colorectal cancer including 6 stage Ⅰ,24 stage Ⅱ,21 stage Ⅲ,and 18 stage Ⅳ patients were enrolled in this study to investigate whether HPV 16 could be involved in colorectal tumorigenesis.Nested-polymerase chain reaction(nested-PCR) was used to detect HPV16 DNA in colorectal tumor tissues and further confirmed by in situ hybridization(ISH).In addition,immunohistochemistry analysis was performed to examine the E6 oncoprotein in colorectal tumors.To verify whether E6 could inactivate the p53 transcriptional function,the levels of p21 and Mdm2 mRNA expression were evaluated by real-time reverse transcription(RT)-PCR.RESULTS:Of the 69 colorectal tumors,HPV16 DNA was detected in 11(16%) by nested-PCR,and HPV16 DNA was present in 8 of the 11(73%) tumors which was confirmed by ISH.The presence of HPV16 DNA in colorectal tumors was not associated with patients' clinical parameters including age,gender,smoking status,tumor site;however,HPV16 infection was more common in stage Ⅰ patients than in late-stages patients(Ⅱ,Ⅲ and Ⅳ).We next asked whether HPV16 infection could be linked with colorectal cancer development.Immunohistochemical data indicated that 8 of the 11 HPV16 DNA-positive tumors had E6 oncoprotein expression.Moreover,we also observed that the adjacent normal tissues including endothelial cells,lymphocytes,fibroblasts,and gland cells in E6-positive tumors had E6 oncoprotein expression.In addition,3 of the 4(75%) E6-positive tumors carrying p53 wild-type had negative immunostaining,but one tumor had less p53 immunostaining.We further examined whether E6-positive and/or p53 mutated tumors reduce p53 transcriptional activity.Real-time RT-PCR analysis indicated that p21 and mdm2 mRNA expression levels in E6/p53-wildtype tumors were significantly lower than in their adjacent normal tissues;as expected,E6-positive/p53-mutated tumors had lower p21 and mdm2 mRNA expression levels compared with their adjacent normal tissues.These results clearly indicate that the E6 oncoprotein expressed in p53 wildtype tumors may reduce p21 and mdm2 expression via p53 inactivation.CONCLUSION:These results suggest that HPV16 infection may be involved in a subset of colorectal cancer,and we suggest that the transmission of HPV to the colon and rectum might occur through peripheral blood lymphocytes.

COMPARISON BETWEEN IMMUNOFLUORESCENCE AND PCR IN DETECTING HUMAN PAPILLOMA VIRUS IN CONDYLOMA ACUMINATA

Objective To compare the effectiveness of immunofluorescence and polymerase chain reaction （PCR） in detecring human papilloma virus （HPV） in condyloma acuminata （CA）. Methods HPVs in CA tissues from 60 patients were detected by immunofluorescence and PCR, respectively. Different subtypes of HPVs were also identified with restriction fragment length polymorphism （RFLP） . Resuits The positive detective rates of immunofluorescence and PCR were 56. 67 % （34/60） and 96. 67 % （58/ 60）, respectively （ P 〈 0. 01 ）. RFLP results showed HPV6 and HPV11 were the main subtypes in the detected virus, which accounted for 98.28%. Conclusion The sensibility of PCR is superior to that of immunofluorescence.

Detection of Human Papilloma Virus Type 16 E6 mRNA in Laryngeal Squamous Cell Carcinoma by In Situ Hybridization

Objective：Laryngeal squamous cell carcinoma（LSCC） is a common malignant tumor in Northeast China and is frequently associated with well-established risk factors like smoking and alcohol abuse.Human papilloma virus（HPV） is an epitheliotropic oncogenic virus that has been detected in a variety of head and neck tumors including LSCC.This retrospective study was to investigate the prevalence of HPV infection in patients with LSCC.Methods：In situ hybridization was performed in 99 patients with LSCC to detect the expression of HPV-16 E6 mRNA.Results：The positive rate of HPV16 E6 mRNA was 36.36%（36/99） in laryngeal squamous cell carcinoma（LSCC）,whereas only 3 of 50（6%） specimens of the normal laryngeal mucosa as a control group showed positive results（P0.05）.Additionally,there was no corelation between HPV16 and age,gender,clinical stage,nodal status and tumor site（P0.05）.Conclusion：The results suggest that the increased prevalence of HPV infection compared to normal laryngeal mucosa and the fact that high-risk HPV types（especially type 16） were the most frequently identified do not allow the exclusion of HPV as a risk factor in laryngeal squamous cell carcinoma.However,their clinical value remains to be further investigated.

Detection of Human Papillomavirus DNA in Oral Cancer Tissue Using Polymerase Chain Reaction

Using polymerase chain reaction (PCR), 25 specimens from 22 patients with oral carcinomas were examined by 6 selected primers of human papillomavirus (HPV). Eighteen of the 22 patients (18/22) gave positive reaction with a positive rate of 81.8%. The positive rates of HPV 6, 11, 16 and 18 were 27.3%, 18.2%, 63.6% and 40.9% respectively. 13.6% positive for mixed infection of HPV 16 and 18 (3/22) and 18.2% positive for mixed infection of HPV, 6, 11, 16 and 18 (4/22). Examining enlarged cervical lymph nodes in three cases with suspecting metastases to cervical lymph nodes from oral carcinomas. It revealed HPV DNA 16 and 18 in two cases and HPV DNA 18 in one case. These results suggested that there was a tendency for HPV 16 and 18 to metastasinze via lymphatics. Only one case of the three had a pathologic diagnosis of lymph node metastasis. Of the 30 non tumor controls, HPV DNA positivity was 10%, all being HPV 18. χ 2 test gave a P<0.005. It strongly indicated that HPV 16 and 18 were related to oral carcinomas.

The effect of human papilloma virus type 16 E7 protein expression on growth of RMA cells in vitro and in vivo

Objective： The aim of this study was to study the effect of human papilloma virus （HPV） type 16 E7 protein ex- pression on growth of RMA cells in vitro and in vivo. Methods： The recombination vector pcDNA3.1-E7 carrying wild type HPV 16 E7 was identified by sequencing. The recombination vector pcDNA3.1-E7 was transfected into mouse lymphadenoma cell line RMA by liposome, and the monoclonal cells transfected stably were obtained by antibiotics G418 sieving and limiting dilution assay. RT-PCR method was used to detect the expression of HPV 16 E7 mRNA in RMA-E7 cells. The growth of RMA cells and RMA-E7 cells cultured in vitro was tested by Cell Count Kit-8. RMA-E7 cells and RMA cells were subcutaneously inoculated in syngeneic mice respectively, the tumor size was measured by sliding caliper twice a week, and the E7 protein expression in tumor tissue of mice was detected by Western blot after tumor formation. The kinetics of cytolytic activity of E7 specific T cells in tumor-bearing mice was measured by LDH kit. Results： Sequencing of recombination vector showed the target gene which was inserted into the recombinant was correct, and RMA-E7 cells expressing E7 protein stably were obtained by limited dilution assay. There were no obvious differences in morphous and growth velocity between RMA cells and RMA-E7 cells in vitro. RMA-E7 cells grew in syngeneic mice were significantly slower than RMA cells. The E7 protein was ex- pressed stronger in RMA-E7 cells in vivo than in vitro. The cytolytic ability of ET-specific CTL was activated at the early stage, reached the maximum at the middle stage, and lost at the end stage. RMA-E7 cells isolated from the tumor-bearing mice were more resistant to E7-specific CTL killing than RMA-E7 cells cultured in vitro. Conclusion： The E7 protein expression has no obvious influence on growth of RMA-E7 cells in vitro, and can suppress growth of RMA-E7 cells in vivo. The activity curve of E7 specific CTL approximately presents ＂bell＂ shape. The RMA-E7 cells grew in vivo had a high expression levels of E7 protein, and more resistant to E7-specific CTL killing than those cultured in vitro. The E7 protein expression in vivo not only initiates immune activation, but also induces immune tolerance.

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.

Human papilloma virus vaccination: Review article and an update

Human papilloma virus （HPV） is sexually transmitted and associated with uterine cervix, vaginal, and vulvar cancers in females, oropharyngeal and anal cancer in both genders, and penile cancer in males. Moreover, genital warts are benign tumors which are HPV-related and can occur in both genders. This is a review of HPV structure, HPV infection transmission, the global impact of HPV and its associated diseases, HPV vaccines and their efficacy and safety, public acceptance of HPV vaccines, the obstacles for its acceptance and strategies to address the barriers. Cervarix （a bivalent vaccine with protection against HPV types 16 and 18） and Gardasil （a quadrivalent vaccine with protection against HPV types 6, 11, 16 and 18） are 2 recommended vaccines. The longest follow up of 9.4 years has shown effcacy and protection of the vaccine against HPV types 16 and 18. The adverse effects have been minimal and the vaccine is considered safe. Numerous studies are conducted to follow the vaccinated individuals to better understand the effect of HPV vaccine on incidence of HPV-related cancers and precancerous lesions.

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.

福建省泉州市大学生HPV疫苗接种情况与认知调查

目的:分析福建省泉州市大学生对人乳头瘤病毒(Human Papilloma Virus,HPV)疫苗的接种意愿、接种情况及认知状况,为HPV疫苗的接种与推广提供参考依据。方法:于2023年2月-2024年2月,选取泉州市500名在校大学生进行问卷调查,并分析相关数据。结果:泉州市愿意接种HPV疫苗的大学生占比为47.6%,其中女生96.2%,男生3.8%,且在年龄分布、专业背景以及是否有过性生活等方面的差异有统计学意义(p <0.05)。70.0%的大学生表示听过HPV疫苗或HPV病毒,且接种率达22.2%;92.4%的大学生认为接种HPV疫苗后完全受益,但仍有76.4%的大学生担心HPV疫苗安全性。结论:泉州市大学生对HPV疫苗接种的认知度以及疫苗接种率偏低,建议相关部门或学校应加强大学生健康教育,降低疫苗价格,提高学生对HPV的认知水平。

Squamous Papilloma:Case Report and Review of Literature

Squamous papillomas are common lesions of the oral mucosa with a predilection for the mucosa of the hard and soft palate. As an oral lesion,it raises concern because of its clinical appearance,which may mimic exophytic carcinoma,verrucous carcinoma or condyloma acuminatum. Its pathogenesis is related to human papilloma virus but there is controversy regarding its viral origin. We present a case of squamous papilloma presenting as oral lesion along with a review of the literature.

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.

基于CiteSpace的人乳头瘤病毒疫苗相关研究热点及趋势分析

目的通过对公开发表的人乳头瘤病毒(human papilloma virus,HPV)疫苗相关文献的分析,了解HPV研究热点及趋势,为应用文献计量法分析各领域研究进展和方向提供参考。方法收集中国知网、万方数据库2012-2021年公开发表的HPV疫苗相关中文论文,根据纳入和排除标准纳入相关文献,用CiteSpace 6.1 R6进行作者合作网络、机构合作网络、关键词共现、关键词突发性探测、关键词聚类分析,绘制关键词时间线图。结果2012-2021年,HPV疫苗研究受到关注,相关文献数量整体呈上升趋势,研究热点在宫颈疾病,HPV基因分型及相应疫苗研制,疫苗认知、接种意愿及其影响因素。其中,2012-2014年,关注宫颈疾病、基因分型、预防性疫苗和治疗性疫苗的研究较多,2017-2018年,关注九价HPV疫苗的研究较多,2019-2021年,关注女大学生等特定人群的研究较多。通过关键词时间线图还发现,自2016年HPV疫苗在中国内地上市以后,除传统研究热点,相关研究开始关注HPV疫苗的卫生经济学评价,紧密结合当时的卫生政策背景和卫生热点,涉及医学伦理、心理学等多学科内容,且开始探索当下较为热门的研究方法,研究内容不断丰富和细化,内涵不断深化,外延持续拓展。结论考虑该类研究的与时俱进,未来研究可能会随着疫苗本身的发展,分层研究不同人群接种意愿,提升HPV疫苗覆盖率的接种策略,覆盖更多亚型的多价疫苗研制、效果、安全性、成本效益研究,HPV疫苗接种相关的真实世界研究,以及一系列疫苗推广和信息化等管理措施的效果评价。

人乳头瘤病毒多基因型检测对传统部分基因型宫颈癌筛查策略价值优化的敏感性分析

目的评估薄层液基细胞学检查(thinprep cytologic test,TCT)筛查技术的有效性、部分宫颈癌诊断费用和初始人群中人乳头瘤病毒(human papilloma virus,HPV)低度风险基因型感染者占比对HPV多基因型和HPV部分(16/18)基因型检测初筛策略的成本效果影响,为公共卫生决策部门选择宫颈癌筛查策略提供参考。方法基于构建的Markov队列模型,以预防宫颈癌发病例数为效果指标,模型运行50年,对HPV多基因型和HPV部分(16/18)基因型筛查方案进行敏感性分析,分析TCT筛查技术的有效性、部分宫颈癌诊断费用,以及初始人群中HPV低度风险基因型感染者占比的变化对成本效果的影响。结果在设定的模型及各参数阈值下,敏感性分析发现:HPV低度风险基因型(HPV 51/35/39/68/56/59/66型)感染者(HPV感染状况或进展为CIN1/2/3状况)中TCT分流检测的灵敏度与特异度[以TCT结果为不典型鳞状上皮细胞病变(atypical squamous cells of undetermined significance,ASCUS)以上为判别标准]变化对两种筛查策略差距影响较大;TCT检测费用、阴道镜检测费用及组织病理学检测费用对两种筛查策略差距影响相对较小。上述各指标在设定阈值范围内变化时,HPV多基因型与部分基因型策略相比,效果差异甚微,成本差异有所变化,具有成本优势。此外,随着初始人群中HPV低度风险基因型感染者的比例增大,HPV多基因型策略的优势亦逐渐增强。结论进一步明确HPV不同基因型的致病风险对优化多基因型HPV筛查的后续管理路径具有重要意义,而进一步细分TCT检测的TBS(The Bethesda System)分级报告结果,提升TCT检测精度则是保障多基因型HPV筛查防治策略价值优化的关键。

人乳头瘤病毒多基因型检测对传统部分基因型宫颈癌筛查策略的价值优化:基于Markov模型的分析

目的比较人乳头瘤病毒(human papilloma virus,HPV)多基因型(extended genotyping)与HPV部分(16/18)基因型检测技术对宫颈癌筛查策略及其后续管理的影响,分析可能带来的价值变化。方法基于Markov队列模型,以预防宫颈癌发病例数为效果指标,模拟100万名初始年龄为15岁的健康妇女在10、20、30、40、50年内从健康状态到宫颈癌发病的疾病进程,基于2种检测技术的宫颈癌筛查-诊断-癌前病变诊疗路径构建模型,分析2种筛查技术不同累计年份下的效果指标、阴道镜检查次数、宫颈上皮内瘤样病变(cervical intraepithelial neoplasia,CIN)1/2/3状态的筛查率,并比较成本与成本效果,以此判定对价值的影响。结果模型模拟10、20、30、40、50年,HPV多基因型相对于HPV部分(16/18)基因型在成本上分别减少29.73万、75.55万、98.53万、111.23万、119.39万元,效果始终保持一致,阴道镜检测次数可分别减少1002、2726、3865、4605、5086人次,CIN1-3筛查率上,模型运行第10、20、30、40、50年时,HPV多基因型策略分别减少约4%的CIN1-3的筛查率。结论相比于HPV部分(16/18)基因型,HPV多基因型检测技术在保障预防效果的情况下,能降低筛查假阳性带来的阴道镜“过诊”率,提升阴道镜检查精度,优化卫生资源利用效能,一定程度上避免假阳性带来的心理负担,从而优化传统HPV部分(16/18)基因型的筛查价值。