Safety and immunogenicity of human papillomavirus-16/18 AS04-adjuvanted vaccine in healthy Chinese females aged 15 to 45 years:a phase Ⅰ trial

Globally,about 70% of cervical cancers are associated with human papillomavirus (HPV)-16 or HPV-18 infection.A meta-analysis of epidemiologic studies in China showed that HPV was present in 98% of cervical cancer samples.The HPV-16/18 AS04-adjuvanted vaccine Cervarix has shown a high level of protection against HPV-16/18 infections and associated cervical lesions.This phase Ⅰ trial (NCT00549900) assessed the safety,tolerability,and immunogenicity of the vaccine in Chinese.Thirty healthy Chinese females,aged 15 to 45 years with a median age of 29.5 years,received three doses of Cervarix in Months 0,1,and 6.Safety was assessed via recording solicited local and systemic symptoms within 7 days and unsolicited symptoms within 30 days after each vaccination.Serious adverse events,new onset of chronic diseases,and other medically significant conditions were recorded throughout this trial.As an exploratory objective,HPV-16/18 antibody titers were determined by enzyme-linked immunosorbent assay in serum samples collected in Months 0 and 7.Pain at the injection site was the most frequently reported local symptom.Two subjects reported medically significant adverse events.Both cases were assessed as unrelated to vaccination by the investigator.In Month 7,100% seroconversion was observed for both anti-HPV-16 and anti-HPV-18 with high geometric mean antibody titers.HPV-16/18 AS04-adjuvanted vaccine,evaluated for the first time in Chinese females,was generally well tolerated and immunogenic,as previously shown in global studies.

Human Papilloma Virus Vaccine Acceptability and Its Associated Factors among Mothers of Female Children 9 - 14 Years in Ndola District of Zambia

Zambia has the second-highest incidence of HPV-related cervical cancer in sub-Saharan Africa, with a rate of 53.7 per 100,000 women, despite the availability of prophylactic HPV vaccines targeting HPV types 16 and 18. As parental consent is often required for adolescent vaccinations, understanding the factors influencing parental acceptance is essential. This study aimed to assess the acceptability of the human papillomavirus (HPV) vaccine and its associated factors among mothers of female children aged 9 - 14 years in Ndola, Zambia. This cross-sectional survey involved 350 mothers from selected townships in Ndola District and utilized multivariable logistic regression to analyze data. The findings revealed an HPV vaccine acceptability rate of 61.8%. Key factors influencing vaccine acceptance included knowledge of HPV, occupational status, and alcohol consumption. Mothers who had knowledge of HPV were 2.41 times more likely to accept vaccination for their daughters [AOR 2.41 (95% CI: 1.63 - 3.62)]. Employment status also played a significant role, with employed mothers being 1.47 times more likely to accept the vaccine [AOR 1.47 (95% CI: 1.02 - 2.13)]. Additionally, mothers who did not consume alcohol were 1.81 times more likely to accept the vaccine for their daughters [AOR 1.81 (95% CI: 1.22 - 2.66)]. We conclude that the HPV vaccine acceptability rate in Ndola, Zambia, remains suboptimal. This underscores the need for targeted interventions, such as public health campaigns and educational programs, to improve HPV vaccine knowledge and acceptance, particularly among specific demographic groups. Enhancing understanding of the HPV vaccine’s benefits could contribute to reducing the high burden of cervical cancer in Zambia.

A study on the cognitive status of human papillomavirus among adult males in Tianjin based on the health belief model

Background:To understand the health beliefs and knowledge of human papillomavirus among adult males in Tianjin.Methods:An online questionnaire survey was conducted from 18 January 2023 to 6 March 2023 using snowball sampling method.Analyze the health belief scores and human papillomavirus(HPV)and HPV vaccine knowledge scores of adult males in Tianjin,and analyze their influencing factors.Results:A total of 388 adult males in Tianjin were surveyed,with an average total score of 3.23±0.04 for their health beliefs.Among them,the average scores for perceived severity,perceived susceptibility,perceived impairment,perceived benefit,and self-efficacy were 3.41±1.05,2.37±1.20,2.96±1.00,3.51±0.90,and 3.36±1.08,respectively.Multiple linear regression analyses showed education was a factor influencing health beliefs.The average total score of knowledge is 64.09±15.62,with 277 people scoring above 60,and a pass rate of 71.4%.Through multiple linear regression analysis,education level,emotional status,whether disease testing has been done,and whether family and friends have been diagnosed with HPV positive are the main influencing factors.Conclusion:The awareness rate of HPV among adult males in Tianjin is still acceptable,but there are still misconceptions.The overall level of health beliefs is moderate,and the perceived susceptibility level is low.It is necessary to strengthen health education on HPV related knowledge for males and improve their cognitive level.

Study on the Correlation between Human Papillomavirus and Mycoplasma genitalium Combined with TCT Detection

Objective: This study aims to explore the correlation between human papillomavirus (HPV) and Mycoplasma genitalium (CT) combined with TCT detection in cervical cancer screening. Method: A cross-sectional study design was adopted, and a total of 609 women who came to seek medical treatment were recruited as the study subjects. Combination testing was evaluated on cervical cancer screening by testing the women for HPV, CT with TCT detection and analyzing the relationship of cervical lesions with HPV and CT infection. Results: The study results showed that 21.57% of the subjects were infected with both HPV and CT, and 48.42% of the cases had abnormal TCT results at the same time. Further data analysis showed that HPV infection was significantly associated with abnormal TCT outcomes (p < 0.05), suggesting a possible synergistic effect of the two infections in cervical lesions. The combined sensitivity and specificity of HPV, CT and TCT detection were 21.57% and 48.42%, respectively, which were significantly higher than that of single detection. Conclusion: In summary, the results of this study support the importance of combined HPV, CT, and TCT testing in cervical cancer screening, and propose the hypothesis that combined testing may improve screening effectiveness. However, further large sample studies are needed to confirm this conclusion and explore the prospects of combined testing in clinical practice.

Evaluating the Association between Human Papillomavirus and Vulvar Cancer:A Comprehensive Analysis Using Bradford Hill Criteria

Background:The role of human papillomavirus(HPV)in the development of vulvar cancer(VC)has been widely studied,but findings have been inconsistent.Despite numerous meta-analyses exploring the potential link between HPV and VC,the association remains controversial due to inherent limitations in meta-analytic methods.Objectives:To address this controversy,the study aims to investigate the potential link between HPV and VC using the Bradford Hill criteria,which offer a more comprehensive framework for establishing causation.Methodology:The study began by extracting all relevant studies on the association between HPV and VC from the PubMed database.The potential links were then assessed by examining the data using the major postulates of the Bradford Hill criteria.To ensure the reliability of the findings,the methodologies of the identified studies were critically evaluated to account for possible false-negative and false-positive results.Results:The assessment of previous studies against the Bradford Hill criteria revealed that the major postulates were not fulfilled.Conclusion:Based on the findings,it can concluded that there is no causal association between HPV and VC.

Monoarthropathy or Polyarthritis in Adolescent Japanese Girls Who Received Immunization with the Human Papillomavirus Vaccine

Joint pain or arthralgia is a common complaint among girls who have received immunization with the human papillomavirus (HPV) vaccine, but the pathogenesis of this disorder has not been completely understood. We report 2 cases of joint lesions after HPV vaccination. In one case, a 13-year-old patient showed transient arthropathy in the right wrist joint after the first dose of Gardasil® administered in her left shoulder. In the other case, an 18-year-old patient had migrating joint pain with redness and swelling after the third dose of Cervarix®. Her serum C-reactive protein and anti-MMP-3 levels were slightly elevated, but no autoantibodies, including rheumatoid factor and anti-CCP antibody, were detected. Although various nonsteroidal anti-inflammatory drugs produced no relief, small doses of both tacrolimus and prednisolone were highly effective for her polyarthritis. The development of reactive joint lesions after HPV vaccination was noteworthy.

PRELIMINARY STUDY OF A NOVEL HUMAN PAPILLOMAVIRUS TYPE 16 L1/E6-E7 CHIMERIC RECOMBINANT DNA VACCINE

Objective Preparations of HPV16 L1/E6 and L1/E7 prophylactic and therapeutic DNA vaccines. Methods The nucleotides within HPV16 E6 and E7 genes, which are responsible for viral transforming activity, were mutated by mage primer site-directed mutagenesis method. The correctly mutated E6 and E7 fragments were separately cloned into an eukaryotic expression vector pVAX1, together with HPV16 L1 gene, generating chimeric recombinants plasmids 1MpVAX1-L1E6, 2MpVAX1-L1E6, 1MpVAX1-L1E7, 2MpVAX1-L1E7 and 3MpVAX1-L1E7. CHO cells were transiently transfected with the individual DNA vaccines by calcium phosphate method. Target protein expressions in the extracts of the transfected cell lines were measured by ELISA and immunohistochemistry, with HPV16 L1 and E6 specific monoclonal antibodies. Results ELISA assays showed the P/N ratios in the cell extracts transfected with L1E6 and L1E7 plasmids were more than 2.1. Immunohistochemistry revealed brownish precipitant signal in cytoplasm and nuclei of the transfected cells. Conclusion Successful constructions of prophylactic and therapeutic DNA vaccine plasmids lay solid foundation for future animal experiment and clinical trial.

SEARCH FOR HERPES SIMPLEX VIRUS TYPE2（HSV－2）AND HUMAN PAPILLOMAVIRUS（HPV）IN THE NORMAL AND ABNORMAL CERVICAL SAMPLES

The specimens of 111 cervical carcinomas. 68 chronic cervicitis and 43 normal cervical exfoliated epithelial cells were examined for the presence of HSV2 DNA sequences with DNA hybridization using HSV2 BgL Ⅱ N fragment probe labelled by 32PdCTP. The result showed that the infection rates of HSV2 in the samples of cervical cancer.chronic cervicitis and normal epithelial cells were 1 4. 41 %(16/111). 27.94%( 19/68) and 25.58% ( 11/43),respectively. It was implied that early stages carcinogenesis of cervical epithelial cells might be correlated with the HSV2 infection.Sixteen HSV 2 positive samples of cervical carcinomas were also examined for the presence of the sequences homologous to human papillomavirus (HPV) type 6B/11. 16 and 18 DNA using dot blot hybridization (Tm17℃). The result indicated that 13 out of 16 were HPV 16 DNA hybridization positive accounting for 81. 2% of all HSV-2 positive samples and none of them were positive for HPV type 6B/11 and 18. The result indicated that double infection of HSV 2 and HPV16 in the same cervical carcinoma tissues may provide a strong evidence of the viral synergistic interaction in the induction of female cervical

治疗性HPV疫苗研究开发策略专家共识

人乳头瘤病毒(HPV)是双链DNA病毒,高危HPV感染易引发宫颈癌及癌前病变风险。近年来,已有超过400多种不同亚型的HPV被鉴定出,大多数HPV感染是无症状的,可以自行消退。免疫系统正常的女性,从感染高危HPV开始,通常需要15~20年才能发展为宫颈癌;但是对于免疫系统较弱的女性,如未经治疗的HIV感染女性(WLHIV),宫颈癌可能发展得更快(可能5~10年)。2006年,预防性HPV疫苗研发上市,但对已感染HPV或癌前病变患者无治疗效果。治疗性HPV疫苗的开发可为目前预防和治疗宫颈癌的方法提供重要的补充。与预防性HPV疫苗不同,治疗性疫苗旨在诱导特异性细胞免疫而非体液免疫(中和抗体),用于清除或治疗现有的HPV感染及其引起相关的癌前病变和侵袭性宫颈癌。因此,制定合理的治疗性HPV疫苗开发策略,不仅可以让治疗性HPV疫苗产品开发企业少走弯路,提高转化效率,而且可以使HPV感染及相关病变甚至癌变患者及早受益。本课题组织领域内专家学者,参考有关文件,结合HPV临床特点和发展背景,特别编撰了《治疗性HPV疫苗研究开发策略专家共识》,明确了适应范围、相关术语等,重点阐述了治疗性HPV疫苗临床开发方向、研究人群及特性和接种规划,旨在加快和推进治疗性HPV疫苗的研发,为社会研究开发治疗性HPV疫苗产品以及国家制定治疗性HPV疫苗相关政策提供借鉴和参考。

备孕女性HPV筛查及其疫苗接种状况调查

目的:调查备孕女性人乳头瘤病毒(HPV)感染情况并分析HPV疫苗接种影响因素。方法:收集2022年1月-2023年1月本院健康检查的211例备孕女性宫颈样本,采用聚合酶链式反应-反向点杂交法进行HPV感染亚型分型,通过问卷调查备孕女性HPV疫苗接种情况,分析影响备孕女性HPV疫苗接种影响因素。结果:备孕女性HPV感染率为22.7%,其中高危型HPV感染率为81.25%,主要HPV感染亚型为HPV52(18.8%)、HPV16(10.4%)。HPV单一型感染率为20.6%,多重感染率为14.6%。211例HPV疫苗接种率为14.7%,文化水平低、不知道HPV疫苗是影响备孕女性HPV疫苗接种的影响因素(P<0.05)。结论:本次调查的备孕女性HPV感染率为22.7%,以HPV52、HPV16为主要感染亚型;HPV疫苗接种率较低,应加强对备孕女性相关知识宣传,提高HPV疫苗接种率。

7345例女性HPV感染状况及亚型分布特征分析

目的了解于日照市中医医院就诊的女性人乳头瘤病毒(HPV)感染状况及基因型分布特征,为宫颈癌早期筛查防治、疫苗接种提供数据参考。方法收集2020年1月至2022年12月于日照市中医医院行HPV基因分型的7345名女性的检测结果,分析总体及不同年龄组的HPV感染率、基因型分布及疫苗保护的HPV基因型感染情况。结果在7345份检测标本中,检测出阳性标本1563份,阳性率为21.28%。其中来自妇科门诊的标本阳性率25.54%(1097/4295),来自健康中心的标本阳性率15.28%(466/3050),门诊标本阳性率明显高于健康中心的标本阳性率,差异有统计学意义(χ^(2)=112.13,P<0.05)。单一高危型感染率为11.79%(866/7345),多重分型感染率为5.62%(413/7345)。感染率最高的5种高危型依次是HPV16(3.89%)、HPV52(3.05%)、HPV58(2.06%)、HPV 53(1.97%)、HPV 31(1.54%)。HPV感染率在年龄分组分析中出现两个高峰,分别为≤20岁组(39.06%)和≥61岁组(27.24%)。HPV九价疫苗涵盖的基因型感染占比为64.43%。结论于日照市中医医院就诊的女性HPV感染率为21.28%,以单一高危型感染为主,青少年女性感染率最高,适龄女性推荐选择九价疫苗。

HPVL1壳蛋白及p16蛋白在高危型HPV持续感染的宫颈低级别鳞状上皮内病变患者临床转归中的意义

目的探讨人乳头瘤病毒(human papilloma virus,HPV)L1壳蛋白及p16蛋白在高危型HPV持续感染的宫颈低级别鳞状上皮内病变(low-grade squamous intraepithelial lesion,LSIL)患者临床转归中的意义。方法选取2022年1月至7月在中山市博爱医院妇科宫颈病变中心就诊的114例高危型HPV持续感染且病理确诊为LSIL患者的宫颈组织进行HPV L1、p16免疫组化分析及随访。结果114例LSIL患者累计进展率21.93%,HPV L1、p16阳性率分别为25.44%、39.47%。单独检测中,HPVL1(+)表达者的消退率最高达68.97%,与进展组、持续组间的差异有统计学意义(P<0.05);联合检测中,HPVL1(+)/p16(+)、HPVL1(+)/p16(–)、HPVL1(–)/p16(+)表达者疾病累计消退率分别为60.00%、78.57%、43.64%,与累计进展率、持续率的差异均有统计学意义(P<0.05)。分层分析发现,单独检测中,HPVL1(+)表达者在第24个月时的消退率高于p16(+)表达者,差异有统计学意义(P<0.05)。联合检测中,HPVL1(–)/p16(+)表达者在第6、12个月时的进展率高于其他患者;而HPVL1(+)/p16(–)表达者在第24个月时的消退率高于其他组,差异均有统计学意义(P<0.05)。二分类Logistic回归分析结果表明,HPV16/18、p16(+)是LSIL进展的危险因素,OR分别为3.242(95%CI:1.261~8.336)、2.714(95%CI:1.055~6.980)。结论高危型HPV持续感染型别分析、HPVL1壳蛋白及p16蛋白免疫组化检测在高危型HPV持续感染的LSIL患者临床转归中有一定临床价值,有助于指导临床医师对高危型HPV持续感染的LSIL患者进行个体化随访及分流管理。

HPV16 E5 Peptide Vaccine in Treatment of Cervical Cancer In Vitro and In Vivo

Human papillomavirus （HPV）-induced cervical cancer is the second most common cancer among women worldwide. Despite the encouraging development of the preventive vaccine for HPV, a vaccine for both prevention and therapy or pre-cancerous lesions remains in high priority. Thus far, most of the HPV therapeutic vaccines are focused on HPV E6 and E7 oncogene. However these vaccines could not completely eradicate the lesions. Recently, HPV E5, which is considered as an oncogene, is getting more and more attention. In this study, we predicted the epitopes of HPV16 E5 by bioinformat- ics as candidate peptide, then, evaluated the efficacy and chose an effective one to do the further test. To evaluate the effect of vaccine, rTC-1 （TC-1 cells infected by rAAV-HPV16E5） served as cell tumor model and rTC-1 loading mice as an ectopic tumor model. We prepared vaccine by muscle injection. The vaccine effects were determined by evaluating the function of tumor-specific T cells by cell prolif- eration assay and ELISPOT, calculating the tumor volume in mice and estimating the survival time of mice. Our in vitro and in vivo studies revealed that injection of E5 peptide＋CpG resulted in strong cell-mediated immunity （CMI） and protected mice from tumor growth, meanwhile, prolonged the sur- vival time after tumor cell loading. This study provides new insights into HPV16 E5 as a possible target on the therapeutic strategies about cervical cancer.

Human Papillomavirus as an Independent Predictor in Oral Squamous Cell Cancer

Aim There is an increasing evidence for the role of high risk human papillomavirus （HPV） in the pathogenesis of oral squamous cell carcinoma （OSCC）. The purpose of this study is to evaluate the relevance of HPV infection to the survival and prognosis of OSCC. Methodology Fifty-two patients with OSCC were followed from 4 to 88 months with a median of 50.7 months. HPV DNA was identified in formalin-fixed, paraffin-embedded tumor specimens by nested PCR with MY09/MY11 and GP5^＋/GP6^＋ primer pairs and the HPV genotype was determined by direct DNA sequencing. Association between the HPV status and risk factors for cancer as well as tumor-host characteristics were analyzed.Survival curves were calculated by the Kaplan-Meier method and analyzed using the log-rank test. Results HPV was found in 40.4% of the tumors with HPV16 accounting for 63.5%, HPV18 for 30.8%, HPV6 for 3.9% and HPVll for 1.8%. No infection with more than one HPV genotype was detected. HPV infection was significantly associated with poor histological grade, TNM stage Ⅰ -Ⅱ, alcohol usage and no smoking status. Multivariate analysis showed that HPV had an independent prognostic effect on the overall survival after adjusting other confounding factors such as histological grade, TNM stage and tobacco usage. The presence of HPV was significantly correlated with a better survival in patients with OSCC. Conclusion HPV infection can act as an independent predictor for the survival and prognosis of OSCC.

HPV16E7-HSP70 Hybrid DNA Vaccine Induces E7-Specific Cytotoxic T Cells and Antitumor Immunity

Using human papillomavirus type 16 （HPV16） E7 as an antigen and Heat Shock Protein 70 as adjuvant, we constructed a DNA vaccine by linking HSP70 gene to E7^C91G; gene. Mice, after being immunized with E7^C91G;-HSP70, E7^C91G/HSP70, E7^C91G, and wild E7 DNA vaccines respectively, produced E7 specific CD8^＋ T-cell precursor frequencies of 280.33±2.52, 144.34±4.04, 164.34±5.13 and 82.33±3.51 respectively within every 1 × 10^5 mouse splenocytes. This proves that E7^C91G-HSP70 fusion vaccine can significantly enhance the E7 specific cellular immunity within the mice body（p〈0. 01）. After being immunized with E7^C91G-HSP70 fusion vaccine, tumor-bearing mice of the group being treated have significantly longer latency and survival periods, comparing with other three categories of E7 vaccines. Experiment shows that this vaccine has a significant effect on enhancing E7 positive tumor-treatment within mice body. After being immunized with E7^C91G-HSP70 vaccine, there were no pathological changes found in livers, kidneys and spleens of the mice, which proves that the vaccine is quite safe. After all, E7^C91G-HSP70 fusion vaccine has a much stronger tumor- treatment effect than thai of wild type E7 DNA vaccine.

CONSTRUCTION AND IMMUNOGENICITY OF HUMAN PAPILLOMAVIRUS TYPE 6B L1 RECOMBINANT PLASMID

To construct a DNA vaccine as a prophylactic model to prevent condyloma acuminatum and detect its immu-nogenicity in mice. Methods The major capsid protein (L1) gene of human papillomavirus (HPV) 6b was inserted into an eukaryotic ex-pression plasmid (pcDNA3.1). The recombinant plasmid was transfected into COS-7 cells. Western blot were performed to detect whether L1 protein can be expressed in eukaryotic cells. Eighteen female BALB/c mice were tested for immunoge-nicity study. Results The recombinant plasmid (pcDNA3.1-HPV6bL1) was verified as HPV6b L1 gene by sequencing. Western blot showed specific strip. Anti-L1 protein antibodies could be detected in the mice’s sera inoculated with pcDNA3.1-HPV6bL1. Similarly, IL-4, IL-2, and IFN-γ were increased in the same mice. Conclusion HPV6b L1 recombinant plasmid was constructed successfully which had immunogenicity for BALB/c mice. It provided experimental evidence for the research of DNA vaccine of condyloma acuminata..-

Apoptosis of HeLa cells inhibited by human papillomavirus type 16 E6 protein interacting with hDaxx

Objective: To study the interaction of human papillomavirus type 16 (HPV16 E6) protein and human death domain associated protein (hDaxx) and its effect on apoptosis of HeLa cells to provide the experimental basis for exploring the oncogenic mechanism of HPV16 E6 protein. Methods: Recombinant vector of pGADT7/E6 or pGBKT7/hDaxx was con- structed. The interaction of E6 protein and hDaxx was detected by yeast two-hybrid system. Their expression in yeast was detected by Western blotting. The eukaryotic plasmids of E6 and hDaxx were co-transfected into HeLa cells. Apoptosis was induced by 5-FU. The apoptotic rate was measured by flow cytometry (FCM). Results: E6 protein had intracellular interaction with hDaxx. The apoptotic rate was rising with the increase in the transfection quantity of pcDNA3.1 (-) / hDaxx in pcDNA3.1 (-) /E6 and pcDNA3.1 (-) / hDaxx co-transfected cells. The difference was significant ( P < 0. 01). Conclusion: There is intracellular interaction between HPV16 E6 protein and hDaxx. The over-expression of hDaxx can increase the sensitivity of E6 protein positive HeLa cells to 5-FU. The effect was in a dose dependent manner. HPV16 E6 protein inhibited the apoptosis of HeLa cells by interacting with hDaxx.

1658例生殖健康门诊男性HPV感染情况及基因型分布特征分析

目的了解生殖健康门诊男性的人乳头瘤病毒(human papillomavirus,HPV)感染情况和基因型分布特征,并比较各年龄组间是否存在差异。方法以2018—2022年在上海计生所医院门诊就诊的1658例男性为研究对象,采用PCR-反向点杂交法对23种HPV基因型进行检测。结果研究对象的HPV总感染率为22.50%。主要感染类型为单一感染(66.76%)。各年龄组HPV感染率的差异具有统计学意义(P<0.001),18~30岁、31~40岁、41~50岁和51岁及以上组HPV感染率分别为16.83%、22.87%、34.63%和29.35%。感染率居前5位的高危型HPV为HPV52(3.56%)、HPV16(3.26%)、HPV39(2.41%)、HPV51(2.17%)和HPV58(2.17%)。感染率最高的低危型HPV为HPV81(2.90%)。本研究中感染者的全部基因型能被HPV二价、四价、九价疫苗覆盖的比例分别为7.77%、12.33%和26.27%。结论本地区生殖健康门诊男性研究对象HPV感染类型以单一感染为主。高危基因型感染以HPV52、16、39、51和58最常见,低危基因型感染以HPV81最常见。41~50岁男性受检者的HPV感染率较高。

基于ARIMA模型的天津地区单中心HPV感染趋势及基因型特征

目的采用自回归移动平均(ARIMA)模型构建时间序列,分析天津地区单中心人乳头瘤病毒(HPV)感染趋势及基因型特征。方法选择2018年1月-2022年12月某院进行HPV检测的7236例女性患者,比较2018-2022年天津地区HPV感染情况及基因型分布。建立ARIMA模型时间序列,分析模型拟合。预测2023年HPV感染数,并与实际发生数进行比较,评价模型的预测效果。结果2018-2022年天津地区HPV感染率为14.41%;HPV感染率在31~40岁年龄段最高,感染率为15.47%。阳性标本中HPV单一型别感染比率最高,占比为73.54%(767/1043),以高危型HPV为主。低危型感染占比最高的是HPV-6型,为2.59%,高危型感染占比最高的是HPV-16型,为16.06%。建立ARIMA模型,确定最佳模型为ARIMA(0,1,2)(0,1,1)12,其AIC值和BIC值分别为3.877、4.005,经白噪声检验Ljung-Box Q=8.828差异无统计学意义(P>0.05)。利用模型预测2023年HPV感染数,实际值、预测值的总体趋势基本保持一致,模型RMSE、MAPE、MAE分别为6.289、34.149、4.706,提示模型的预测效果较好。结论天津地区女性人群中,HPV病毒感染类型以单一高危型感染为主,其中HPV-16型感染率最高。天津地区HPV感染存在季节性,ARIMA模型在HPV感染流行趋势的预测中效果较好,适用于短期预测。

Reid阴道镜评分、HPV E6/E7 mRNA表达量在宫颈癌中的临床应用价值研究

目的研究Reid阴道镜评分(以下简称Reid评分)、高危型人乳头瘤病毒(HR-HPV)mRNA表达量与宫颈癌国际妇产科联盟(FIGO)分期、血清常规肿瘤标志物水平的相关性及对宫颈癌术后淋巴结转移的预测价值。方法选取2021年3月至2022年5月在菏泽市立医院就诊的100例宫颈癌患者作为宫颈癌组,另选同期诊治的50例低级别鳞状上皮内病变(LSIL)患者作为LSIL组,50例高级别鳞状上皮内病变(HSIL)患者作为HSIL组。比较3组Reid评分、HPV E6/E7 mRNA表达量及血清常规肿瘤标志物[糖类抗原125(CA125)、癌胚抗原(CEA)]水平;分析宫颈癌组Reid评分、HPV E6/E7 mRNA表达量与血清常规肿瘤标志物水平及宫颈癌FIGO分期的相关性;根据宫颈癌组患者术后随访结果分为术后有淋巴结转移和无淋巴结转移,比较有无淋巴结转移患者Reid评分、HPV E6/E7 mRNA表达量及血清CA125、CEA水平,分析Reid评分、HPV E6/E7 mRNA表达量对宫颈癌术后淋巴结转移的预测价值。结果宫颈癌组Reid评分、HPV E6/E7 mRNA表达量及血清CA125、CEA水平均高于HSIL组、LSIL组(P<0.05);HSIL组Reid评分、HPV E6/E7 mRNA表达量及血清CA125、CEA水平均高于LSIL组(P<0.05)。宫颈癌患者Reid评分、HPV E6/E7 mRNA表达量与血清CA125、CEA水平均呈正相关(r=0.405~0.705,P<0.05)。Reid评分、HPV E6/E7 mRNA表达量与宫颈癌FIGO分期呈正相关(r=0.415、0.501,P<0.05)。宫颈癌组术后淋巴结转移患者的Reid评分、HPV E6/E7 mRNA表达量及血清CA125、CEA水平均高于无淋巴结转移的患者(P<0.001)。Reid评分、HPV E6/E7 mRNA表达量、CA125、CEA预测宫颈癌术后淋巴结转移的曲线下面积(AUC)分别为0.756(95%CI:0.657~0.838)、0.760(95%CI:0.662~0.841)、0.803(95%CI:0.710~0.877)、0.768(95%CI:0.670~0.848)。将CA125、CEA联合检测作为常规预测方案,Reid评分、HPV E6/E7 mRNA表达量、CA125、CEA联合检测作为新预测方案,常规预测方案预测宫颈癌术后淋巴结转移的曲线下面积(AUC)为0.826(95%CI:0.724~0.889),新预测方案预测宫颈癌术后淋巴结转移的AUC为0.955(95%CI:0.892~0.987),新预测方案预测的AUC明显大于常规预测方案(Z=1.981,P=0.045)。与常规预测方案比较,新预测方案的净重新分类指数为0.021(95%CI:0.015~0.039)、综合判别改善指数为0.046(95%CI:0.033~0.069),均P<0.05。结论Reid评分、HPV E6/E7 mRNA表达量与宫颈癌FIGO分期及血清CEA、CA125水平相关,且在预测宫颈癌术后淋巴结转移方面具有一定价值。