高危型人乳头瘤病毒感染与阴道微生态及宫颈局部细胞免疫的相关性

探讨高危型人乳头瘤病毒(HR-HPV)感染与阴道微生态及宫颈局部细胞免疫的相关性, 为该类患者的治疗提供参考。

选择2018年1月至2020年1月我院收治的126例HPV感染者, 依据感染病毒类型分为非HR-HPV感染组(n=69)和HR-HPV感染组(n=57), 并纳入同期来我院体检的50名健康体检者作为对照组。分析HPV感染类型、患者阴道微生态状况及宫颈局部组织T淋巴细胞亚群水平。

患者中复合型与单一型HR-HPV感染率分别为15.8%、84.2%, 差异有统计学意义(χ²=5.324, P=0.047)。对照组、非HR-HPV感染组和HR-HPV感染组对象阴道微生态失调率分别为22.0%、34.8%、45.6%, 其中对照组对象阴道微生态失调率最低(χ²=5.638, P=0.048)。非HR-HPV感染组和HR-HPV感染组患者阴道病原菌检出率高于对照组(均P < 0.05)。非HR-HPV感染组和HR-HPV感染组患者宫颈局部T淋巴细胞亚群水平低于对照组(均P < 0.05)。

HPV33、16、18型为HPV感染主要类型, 会加重阴道微生态紊乱程度, 影响局部细胞免疫功能。检测患者HPV感染情况和宫颈局部细胞免疫功能可为患者临床治疗提供有效数据, 有利于治疗措施的制定。

     

CIN患者阴道微生态状况与HPV感染的关系分析

分析宫颈上皮内瘤变（CIN）患者阴道微生态与人乳头瘤病毒（HPV）感染的关系。

选取326例本院收治的CIN患者,采集阴道分泌物和宫颈脱落细胞,通过形态学和功能学检测阴道微生态状况,采用PCR-反向点杂交法进行HPV分型检测,采用二分类Logistic回归分析影响CIN患者HPV感染的因素。

CIN患者HPV阳性共256例,占78.5%,HPV阴性共70例,占21.5%。HPV阳性CIN患者白细胞计数＞10个/高倍视野、阴道清洁度Ⅲ-Ⅳ度、VVC阳性、AV阳性、BV阳性、pH值＞4.5、白细胞酯酶阳性、过氧化氢阳性占比高于HPV阴性患者,微生态正常者占比低于HPV阴性患者（P＜0.05）。二分类Logistic回归分析显示,VVC、BV、微生态正常和pH值为CIN患者HPV感染的影响因素。

CIN患者HPV感染率较高,且感染后存在阴道微生态失调,VVC、BV、微生态异常和pH值是CIN患者HPV感染的影响因素。

     

跨膜蛋白CD82在流感病毒感染初期的表达

了解细胞跨膜蛋白CD82在流感病毒感染初期的表达变化,分析CD82在流感病毒感染中的作用。

采用逆转录−聚合酶链式反应（RT-PCR）方法对流感病毒感染4 h内的HEP-2细胞中CD82蛋白mRNA表达量进行检测。

流感病毒感染HEP-2细胞后1 h−3 h细胞 CD82的mRNA表达量降低,并且随着流感病毒接种量增加CD82表达量降低持续时间延长。

流感病毒可以在转录水平调节宿主细胞CD82的表达。CD82在流感病毒感染初期表达下降,提示CD82可能在流感病毒与宿主细胞粘附和入侵过程中发挥作用。

     

细菌性阴道炎合并HPV16感染患者阴道菌群分布与局部免疫的关系

探究细菌性阴道炎（BV）合并人乳头瘤病毒16（HPV16）感染患者阴道菌群分布与局部免疫的关系。

选取2019年1月到2023年1月我院收治的83例BV合并HPV16感染患者和81例单纯BV患者,分别作为研究组和对照组,检测两组患者阴道菌群分布和宫颈阴道分泌物中T淋巴细胞亚群（CD4⁺、CD8⁺、CD4⁺/CD8⁺）和炎症因子（IL-1β、IFN-γ、IL-2）水平。

研究组乳酸杆菌数量低于对照组,加德纳菌、大肠埃希菌、无乳链球菌、金黄色葡萄球菌、铜绿假单胞菌、白假丝酵母菌数量高于对照组（P＜0.05）;研究组阴道菌群密集度Ⅲ+Ⅳ级、多样性Ⅱ+Ⅲ级、微生态失调比例均高于对照组（P＜0.05）;研究组宫颈CD4⁺、CD4⁺/CD8⁺比值低于对照组（P＜0.05）;研究组宫颈IL-1β、IFN-γ、IL-2水平低于对照组（P＜0.05）。

合并HPV16感染可使BV患者阴道乳酸杆菌数量减少,阴道微生态失衡,局部免疫功能下降,应尽早检测此类患者阴道菌群和宫颈阴道局部免疫情况,进行针对性干预。

     

基于胶体金标记米曲霉素的免疫层析试纸法快速筛查SLE

建立基于胶体金标记米曲霉素(AOL)的快速筛查系统性红斑狼疮(SLE)的免疫层析试纸法。

利用大肠杆菌BL21原核表达特异性识别核心岩藻糖基的AOL基因(FleA), 并进行纯化及胶体金标记。利用特异性识别IgG的Protein G以及胶体金标记的AOL共同建立快速筛查SLE的免疫层析试纸法(ICS)。

成功表达并纯化AOL重组蛋白, 并进行胶体金标记; 应用胶体金标记AOL的ICS检测SLE患者血清呈阳性反应, 而健康对照及其他自身免疫性疾病(类风湿关节炎、IgA肾病和结缔组织病等)呈阴性反应。

成功建立基于胶体金标记AOL的快速筛查SLE的ICS, 为SLE早期筛查提供了可靠依据。

     

卡介苗荚膜阿拉伯甘露聚糖的提纯鉴定及其免疫调节功能的初步研究

确定卡介苗(BCG)中荚膜中糖成分阿拉伯甘露聚糖(AM)的功能。

本研究从我国目前普遍使用的BCG中, 利用氯仿甲醇抽提方法分离纯化荚膜AM, 经AM单克隆抗体鉴定后, 腹腔注射BCG致敏小鼠, 体内外评价AM的免疫调节功能。

AM能在小鼠体内增强BCG诱导的迟发型超敏反应(P < 0.01), 体外免疫指标检测发现AM提高小鼠脾细胞Th1类细胞因子IFN-γ和TNF-α的表达水平(P < 0.05)。

BCG的荚膜AM是潜在的保护性抗原, 并为优化BCG提供理论依据。

     

妇科门诊阴道镜检查人群阴道微生态改变与人乳头瘤病毒感染的相关性

初步探讨妇科门诊阴道镜检查人群人乳头瘤病毒（human papillomavirus,HPV）感染与其阴道微生态改变的相关性,以了解妇科疾病患者病原体感染与其阴道稳态和生殖道健康的关系。

随机选择2020年4月到2022年4月在我院妇科门诊行阴道镜检查的患者130例,均进行阴道微生态和宫颈HPV检测。根据HPV DNA基因分型结果进行分组,检测HPV感染组和未感染组人群阴道分泌物的清洁度、病原体和阴道微生态相关指标,对阴道微生态改变和HPV感染的相关性进行统计学分析。

130例研究对象中,HPV感染者101例（77.69%）。101例HPV感染者中,以单一感染（76例,58.46%）为主,其中又以单一HR-HPV（high-risk HPV）感染（72例,55.38%）为主。101例HPV感染者中,有21种HPV亚型被检出,排名前5位的亚型分别为HPV16、HPV52、HPV58、HPV53、HPV18,占比分别为16.15%、9.23%、8.46%、6.92%、5.38%。101例HPV感染者和29例HPV未感染者相比,阴道清洁度、阴道pH值、白细胞数量异常、白细胞酯酶活性和唾液酸苷酶阳性率差异均有统计学意义（均P＜0.05）,H₂O₂阳性率组间差异无统计学意义（P＞0.05）。HPV阴性组的阴道乳杆菌异常率及各菌群阳性率均显著低于HPV多重感染组和HPV单一感染组。HPV多重感染组患者乳杆菌异常率、衣原体和解脲脲原体阳性率均高于HPV单一感染组（均P＜0.05）。

阴道微生态失调严重影响患者HPV感染率,且HPV感染与阴道清洁度、菌群密集度、pH值异常和白细胞酯酶阳性率异常有关。

     

高级别上皮内瘤变和不同型别人乳头瘤病毒感染患者阴道微生态特征分析

探讨高级别上皮内瘤变（high level squamous intraepithelial lesion,HSIL）患者阴道微生态的特征及不同型别人乳头瘤病毒（human papilloma virus,HPV）感染对阴道微生态的影响。

收集我院健康女性（对照组,n=54）和HSIL患者（HSIL组,n=54）的阴道分泌物样本,提取其DNA,通过HPV试剂盒检测HPV型别,并使用16S rRNA基因高通量测序分析阴道菌群的组成结构及特征。

HSIL组女性HPV阳性率为88.9%,对照组女性HPV阳性率仅有11.1 %。与对照组相比,HSIL组女性阴道乳杆菌属相对丰度降低,加德纳菌属、普雷沃菌属、双歧杆菌属相对丰度增多,但差异均无统计学意义（均P＞0.05）。与HPV Others组相比,HPV CR组女性阴道阿托波菌属相对丰度显著降低（t=2.067,P=0.043）;加德纳菌属、链球菌属、肠球菌属相对丰度降低,双歧杆菌属相对丰度升高,但差异均无统计学意义（均P＞0.05）。

HSIL患者HPV感染率升高,不同型别HPV感染会对阴道微生态产生影响,提示对阴道微生态进行干预可能对宫颈病变产生调节作用。

     

基于高通量测序分析哮喘小鼠呼吸道菌群的变化

通过高通量测序分析哮喘模型小鼠呼吸道菌群的变化情况。

将12只SPF级BALB/c雄性小鼠随机分为对照组和模型组, 每组6只。采用卵清蛋白致敏方法建立哮喘小鼠模型后, 进行支气管组织切片病理学观察, ELISA法检测血清IgE水平, 测定肺指数, 采集咽拭子后提取DNA行高通量测序分析。

与对照组比较, 模型组小鼠血清IgE水平明显升高(P < 0.05), 肺指数明显上升(P < 0.05), 可见支气管上皮粘膜有水肿, 少量淋巴细胞浸润, 平滑肌增生。模型组小鼠呼吸道菌群与对照组比较, 菌种丰度升高, 厚壁菌门较对照组减少(P < 0.05), 放线菌门和变形菌门增多(P < 0.05), 菌群结构有明显差异。

哮喘小鼠存在呼吸道微生态菌群失衡。

     

成人化脓性脑膜炎患者脑脊液变化

分析成人化脓性脑膜炎患者脑脊液细胞、病原菌等的变化及其关系, 为该病的有效诊断、病情监测和针对性治疗提供参考。

对我院32例成人化脓性脑膜炎患者用药前后不同时期的脑脊液分别进行常规、生化与细胞学检测, 对检测结果进行统计分析。

与恢复期比较, 患者急性期时脑压、脑脊液白细胞总数与乳酸脱氢酶水平显著升高(均P < 0.05)。32例患者中, 15例脑脊液细菌培养呈阳性。典型菌与非典型菌感染者急性期脑脊液白细胞总数、小淋巴细胞、单核吞噬细胞和嗜中性粒细胞比例差异均有统计学意义(均P < 0.05)。

成人化脓性脑膜炎患者脑脊液变化显著, 脑脊液细胞学变化与感染类型相关, 可为个性化诊疗提供参考。

     

细菌性阴道病合并人乳头瘤病毒感染的影响因素

目的 分析细菌性阴道病（BV）合并人乳头瘤病毒（HPV）感染的影响因素,为预防BV合并HPV感染的发生提供参考依据。方法 收集2017年2月至2017年12月就诊于天津中医药大学第一附属医院符合标准的妇女,观察组为HPV合并BV感染的患者,对照组为健康妇女,通过问卷调查研究两组妇女一般情况的差异性。结果 共纳入204名研究对象,其中观察组78例,对照组126例。观察组中HPV感染以单型感染居多,共46例,占59.0%;观察组以高危型别感染居多,共70例,占89.7%。通过单因素回归分析可得年龄≥40岁（P=0.000,OR＝3.795）、初次性生活年龄＜20岁（P=0.011,OR＝2.914）、性伴侣数≥2（P=0.036,OR＝2.005）、每周性生活次数＜2次（P=0.029,OR＝1.927）、妊娠次数≥2（P=0.000,OR＝2.920）是导致HPV合并BV感染的影响因素。多因素非条件logistic回归分析结果显示年龄≥40岁（P=0.001,OR＝3.880）、初次性生活年龄＜20岁（P=0.018,OR＝3.127）、性伴数≥2个（P=0.021,OR＝2.595）、妊娠次数≥2（P=0.030,OR＝2.303）是HPV合并BV的独立影响因素。结论 年龄大、初次性生活年龄小、性伴侣个数多、妊娠次数多为HPV合并BV的独立危险因素,临床中应做好知识普及工作,预防HPV合并BV的发生。     

Prevalence and correlation of human papillomavirus genotypes with clinical factors in cervical samples from Mexican women

In the last decade, the inclusion of HPV DNA testing in cervical cancer screening has provided one of the best strategies for the prevention and timely detection of HPV. We conducted a high-throughput HPV genotyping study based on MALDI-TOF mass spectrometry to determine the prevalence of 24 HPV genotypes, including oncogenic genotypes, in Mexican women and correlated the results with cytological findings and clinical variables. We likewise identified the risk factors in patients with the HPV infection. Our study included 1000 women from Sonora, Mexico, who participated in cervical cancer screening campaigns and who underwent a Pap smear and HPV DNA test. The results showed that the overall prevalence of HPV was 27.2%, 18.5% with single, and 8.7% multiple infections. The low-risk HPV genotype 6 (8.5%) and oncogenic genotypes 31 (8.1%) and 53 (4.4%) were the most prevalent in the study population. The number of lifetime sexual partners, previous STIs, and age at first intercourse was significantly associated with HPV infection (P ≤ 0.05). Smoking (OR = 1.5609; 95% IC 1.062–2.292) and more than three lifetime sexual partners (OR = 1.609; 95% IC = 1.124–2.303) represented risk factors for HPV infection. Cytological abnormalities were found in 3.4% of the HPV-positive samples. CIN 1–3 occurred in 0.6% of high-risk HPV cases. In general, the prevalence of the HPV genotypes is high in Mexican women with normal cytological findings. This issue highlights the importance of HPV research in seemingly healthy women and could help guide screening strategies for cervical cancer prevention in Mexico.Impact statementWe are submitting data regarding the prevalence and type distribution of the HPV infection and the risk factors associated with it, which may provide a valuable reference to reinforce screening strategies, and to maintain HPV genotype surveillance in Mexico. We discuss the overall prevalence of HPV infection as detected in normal cytological samples stratified by age, different types of infection, and oncogenic capacity. One of the most important findings was that common HPV genotypes detected in healthy women were the genotype numbers: 6, 31, 16, and 56, likewise, smoking and having a history of more than three sexual partners over their lifetime, represented the main risk factors in this study. Furthermore, we found a low frequency of cytological abnormalities and CIN 1–3 in women with HR-HPV.     

Association between Free Testosterone Levels and Anal Human Papillomavirus Types 16/18 Infections in a Cohort of Men Who Have Sex with Men

Background

Human papillomavirus (HPV) types 16 and 18 cause invasive cervical cancer and most invasive anal cancers (IACs). Overall, IAC rates are highest among men who have sex with men (MSM), especially MSM with HIV infection. Testosterone is prescribed for men showing hypogonadism and HIV-related wasting. While there are direct and indirect physiological effects of testosterone in males, its role in anal HPV16/18 infections in men is unknown.

Methods

Free testosterone (FT) was measured in serum from 340 Multicenter AIDS Cohort Study (MACS) participants who were tested for anal HPV16/18-DNA approximately 36 months later. The effect of log10-transformed current FT level on anal HPV16/18 prevalence was modeled using Poisson regression with robust error variance. Multivariate models controlled for other HPV types, cumulative years of exogenous testosterone use, race, age, lifetime number of receptive anal intercourse partnerships, body mass index, tobacco smoking, HIV-infection and CD4+ T-cell counts among HIV-infected, and blood draw timing.

Results

Participants were, on average, 60 (+5.4) years of age, White (86%), and HIV-uninfected (56%); Twenty-four percent tested positive for anal HPV16 and/or 18-DNA (HPV16 prevalence=17.1%, HPV18=9.1%). In adjusted analysis, each half-log10 increase of FT was associated with a 1.9-fold (95% Confidence Interval: 1.11, 3.24) higher HPV16/18 prevalence. Additionally, other Group 1 high-risk HPVs were associated with a 1.56-fold (1.03, 2.37) higher HPV16/18 prevalence. Traditional risk factors for HPV16/18 infection (age, tobacco smoking; lifetime number of sexual partners, including the number of receptive anal intercourse partnerships within 24 months preceding HPV testing) were poorly correlated with one another and not statistically significantly associated with higher prevalence of HPV16/18 infection in unadjusted and adjusted analyses.

Conclusions

Higher free testosterone was associated with increased HPV16/18 prevalence measured approximately three years later, independent of sexual behavior and other potential confounders. The mechanisms underlying this association remain unclear and warrant further study.     

Obesity and the likelihood of sexual behavioral risk factors for HPV and cervical cancer

Obesity is associated with higher cervical cancer mortality, but its relationship with sexual behavioral risk factors that predispose women to human papilloma virus (HPV) and cervical cancer is unclear. We used data from 3,329 women participants, aged 20-59 years, of the 1999-2004 National Health and Nutrition Examination Survey, to analyze the relationship between BMI and age at first intercourse, number of sexual partners, condom use during sexual activity, history of sexually transmitted disease (STD), herpes simplex virus 2 (HSV-2) seropositivity, and HPV prevalence. BMI was not associated with the prevalence of HPV. Mildly obese women (BMI 30.0-34.9 kg/m(2)) were least likely to report a STD history (9% vs. 13% in normal weight) and >or=2 sexual partners in the previous year (8% vs. 13%) while overweight women (BMI 25.0-29.9 kg/m(2)) were least likely to report >or=10 lifetime partners; among those with multiple partners, BMI was not associated with sexual activity without condoms in the past month. After adjustment for age, race/ethnicity, and education, women with higher BMI were less likely to report sexual behavioral risk factors than normal-weight women; however, odds ratios were only significant for mildly obese women for reporting a STD history (0.74, 95% confidence interval 0.55-0.99) and having >or=2 sexual partners in the last year (0.57, 0.39-0.85). Higher BMI was not associated with HSV-2 seropositivity after adjustment. HPV and sexual behavioral risk factors for HPV and cervical cancer are not more prevalent in obese than normal-weight women and unlikely to account for higher-observed cervical cancer mortality in obese women.     

Prevalence of DNA-HPV in male sexual partners of HPV-infected women and concordance of viral types in infected couples

Investigation of HPV infection in men remains important due to its association with genital warts and anorectal cancer, as well as to the role men play in HPV transmission to their female sexual partners. Asymptomatic men (n = 43), whose sexual partners had presented cervical HPV infection, were enrolled in this study. Among the 43 men, 23 had their female partner included and tested for HPV-DNA, totaling 23 couples. HPV-DNA was detected by PCR. Type specific PCR to detect HPV 16, 18, 31, 33, 45 and 6/11 was performed. At least one type of HPV was detected in 86.0% (37/43) of the male patients and more than one HPV type was identified in 39.5% (17/43) of the samples, including high and low risk HPV. HPV-16 proved to be the most prevalent viral type in both male and female samples. Concordance of at least one viral type was observed in 56.5% (13/23) of the couples. Among couples that have shown concordance of viral types, 84.6% (11/13) of the men had the same high risk viral type presented by the female sexual partner. These data suggest that HPV infected men is an important reservoir, contributing to a higher transmission to women and maintenance of infection, and consequently, a higher risk of developing cervical cancer. HPV vaccination in men will protect not only them but will also have implications for their sexual partners.     

Behavioral and sociodemographic risk factors for serological and DNA evidence of HPV6, 11, 16, 18 infections

Introduction: Risk for HPV6/11/16/18 infections in young sexually active, behaviorally low-risk females is not well described and may inform public policy. Methods: To assess exposure risk for HPV/6/11/16/18 among 16–23 year old low-risk females, data for 2409 female clinical trial participants were evaluated. Baseline visit self-reported sexual, behavioral and demographic characteristics; and results from HPV genotyping and serology, and other clinical laboratory assays were analyzed. All subjects reported <5 lifetime male sexual partners and no prior abnormal cytology at baseline. Results: While 98% (2211/2255) were naïve to HPV16 or 18 and 99.6% (2246/2255) were naïve for 1–3 index HPVs, 27% (616/2255) showed antibody, DNA or both for ≥1 index HPV. While 18% (409/2255) tested HPV16- or -18-antibody- or -DNA-positive, only 2% (44/2255) tested positive for both types. Against this high background, other sexually transmitted infections (STIs) were uncommonly detected, suggesting low sexual risk-taking behavior. The adjusted analyses showed race, age, alcohol consumption, current Chlamydia trachomatis (chlamydia) and Trichamonas vaginalis (trichomoniasis), bacterial vaginosis (BV), number of lifetime male sex partners predicted positive index-HPV antibody test results. However, only the number of male sex partners predicted positivity for HPV6/11- and 16/18-DNA, and chlamydia infection predicted positivity for HPV6/11-DNA alone. Conclusions: Taken together, type-specific HPV-DNA and -antibody evidence of HPV6/11/16/18 infections among behaviorally low-risk 16–23 year old females is high. Since almost all participants would have benefited by either currently available bivalent or quadrivalent vaccine strategies, delaying vaccination beyond menarche may be a missed opportunity to fully protect young females against HPV6/11/16/18 infections and related dysplasias. Early diagnosis and treatment of chlamydia and trichomonas may be important in HPV pathogenesis.     

268例吸毒女性人乳头瘤病毒感染情况调查及相关高危因素的分析

目的 调查268例吸毒女性人乳头瘤病毒感染情况并分析其相关高危因素。方法 选取我院2016年1月—2018年1月收入的268例吸毒女性作为研究对象,根据是否感染人乳头瘤病毒分为感染组70例及未感染组198例,比较两组吸毒女性基本资料,运用Logistic回归分析模型对具有统计学意义的因素进行分析,总结相关高危因素。结果 268例吸毒女性中人乳头瘤病毒感染者70例,感染率为26.12%且以高危型为主;两组吸毒女性基本资料中除年龄、受教育程度、肿瘤家族病史、盆腔炎病史无明显差异外,其他因素均有统计学意义（P＜0.05）。Logistic回归分析结果显示,免疫功能低下、初次性行为年龄过早（＜18周岁）、多个性伴侣（≥3个）、危险性行为、性伴侣吸毒、长期吸毒（≥3年）为女性吸毒人群人乳头瘤病毒感染的高危因素（OR=4.420、4.551、4.778、4.569、5.110、5.475,Ps＜0.05）。结论 女性吸毒人群人乳头瘤病毒感染率较高且以高危型为主,Logistic回归分析证实,吸毒女性中存在多种高危因素,应该及早针对高危因素采取干预措施。     

Human papillomavirus persistence in young unscreened women, a prospective cohort study

Objective

To evaluate hr-HPV persistence and associated risk factors in a prospective cohort of young unscreened women. Additionally, the relation between hr-HPV status and cytology/histology results is examined.

Methods and Principal Findings

Two year follow-up of 235 out of 2065 young women (18–29 years), participating in a large, one year epidemiological study, with questionnaires, self-collected cervico-vaginal samples (Vibabrush), and SPF₁₀LiPA for HPV detection. Only women hr-HPV positive at sample month 12 were invited for a second year of follow-up. After study follow-up, available cytology/histology data were requested from PALGA (the national network and registry of histo- and cytopathology in The Netherlands). These data were compared with available cytology/histology data of the month 12 hr-HPV negative women from the same cohort. 44.1% of the hr-HPV types detected at study month 12, persisted during follow-up. HPV types 45, 31, 16 and 18 were most likely to persist with percentages of 60.0%, 56.8%, 54.4%,and 50.0%, respectively. Compared to newly detected infections at month 12, infections present since 6 months or baseline had an increased risk to persist (OR 3.09 [95% CI: 1.74–5.51] and OR 4.99 [95% CI: 2.67–9.32], respectively). Other co-factors influencing persistence were, multiple HPV infections, smoking and multiple lifetime sexual partners. The percentage of women with a HSIL/CIN2+ (12.1%) in the persistent HPV group, was not significantly different (p = 0.107) from the 5.3% of the women who cleared the hr-HPV infection, but was significantly (p 0.000) higher than to the 1.6% of women in the hr-HPV negative control group.

Conclusion

We showed that HPV genotype, multiple infections, smoking, and multiple lifetime sexual partners are co-factors that increase the risk of hr-HPV persistency. Most importantly, we showed that hr-HPV infections are more likely to persist the longer they have been present and that women with a persistent hr-HPV infection have a high risk of HSIL/CIN2+ development.     

Sexual Behaviour and HPV Infections in 18 to 29 Year Old Women in the Pre-Vaccine Era in the Netherlands

Background

Infection with Human Papillomavirus (HPV) is a necessary event in the multi-step process of cervical carcinogenesis. Little is known about the natural history of HPV infection among unscreened young adults. As prophylactic vaccines are being developed to prevent specifically HPV 16 and 18 infections, shifts in prevalence in the post vaccine era may be expected. This study provides a unique opportunity to gather baseline data before changes by nationwide vaccination occur.

Methods and Principal Findings

This cross-sectional study is part of a large prospective epidemiologic study performed among 2065 unscreened women aged 18 to 29 years. Women returned a self-collected cervico-vaginal specimen and filled out a questionnaire. All HPV DNA-positive samples (by SPF₁₀ DEIA) were genotyped using the INNO-LiPA HPV genotyping assay. HPV point prevalence in this sample was 19%. Low and high risk HPV prevalence was 9.1% and 11.8%, respectively. A single HPV-type was detected in 14.9% of all women, while multiple types were found in 4.1%. HPV-types 16 (2.8%) and 18 (1.4%) were found concomitantly in only 3 women (0.1%). There was an increase in HPV prevalence till 22 years. Multivariate analysis showed that number of lifetime sexual partners was the most powerful predictor of HPV positivity, followed by type of relationship, frequency of sexual contact, age, and number of sexual partners over the past 6 months.

Conclusions and Significance

This study shows that factors independently associated with HPV prevalence are mainly related to sexual behaviour. Combination of these results with the relative low prevalence of HPV 16 and/or 18 may be promising for expanding the future target group for catch up vaccination. Furthermore, these results provide a basis for research on possible future shifts in HPV genotype prevalence, and enable a better estimate of the effect of HPV 16-18 vaccination on cervical cancer incidence.     

Acquired and genetic susceptibility to cervical cancer

Infection with high-risk human papilloma virus (HPV) is a necessary risk factor for the development of cervical cancer (CC). However, there are many factors that contribute to the development of CC. We have been investigating the role of polymorphisms in chemical metabolizing genes and life-style factors in the development of CC between two countries with significantly different prevalence of CC. Our data confirm that infection with high-risk HPV is the most significant risk factor for CC in both Venezuela and US. In Venezuela, having multiple sex partners and early sexual activities are significant risk factors (OR=4.7, 95% CI=1.7-13.1; OR=6.7, 95% CI=2.3-20.1, respectively). On the other hand, cigarette smoking is the significant risk factor for women in the US (OR=6.4, 95% CI=1.8-23.2). Genotype analyses were conducted using specimens from the US population only. The GSTM1 null genotype was associated with a significant 3.4 fold increase in risk (95% CI=1.0-11.8) compared with those who were GSTM1 positive, after adjustment for smoking and HPV infection. Polymorphosis in CYP2E1 and mEH are associated with a non-significant increase in risk. Our study indicates that different acquired and genetic susceptibility factors can make significant contributions to the development of environmental disease such as cervical cancer.