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Evaluating the association of hormonal contraceptive use with HPV detection in pre- and perimenopausal women in the U.S

机译：在美国评估绝经前和围绝经期妇女使用激素避孕药与HPV检测的关联

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Introduction:.;Long-term and recent use of combined oral contraceptives (COCs) was suggested to be a risk factor of cervical cancer. It is unclear whether the association is driven by COC's effect(s) on carcinogenesis and/or on upstream events of HPV infection, as study findings on the association between hormonal contraceptive use and HPV infection have been inconsistent. Understanding the effect of hormonal contraceptive use on HPV detection and cervical immune milieu in women older than 35 years may provide insight into the biological mechanisms underlying the impact of hormonal contraceptive use on cervical cancer risk.;Objectives:.;A prospective cohort of pre- and perimenopausal females (age range: 35-54) who had normal cervical cytology were followed to investigate the association between cervical HPV detection and hormonal contraceptive use (n=530). The study has 3 aims: Aim 1: To determine the association of hormonal contraceptive use with HPV prevalence at baseline. Aim 2: To compare the odds of new HPV DNA detection between users and non-users of hormonal contraceptives. Aim 3: To describe and compare differences in the host cervical cytokine profiles between hormonal contraceptive users and non-users who were HPV-negative at baseline.;Methods:.;Pre- and perimenopausal women (age range: 35-54 years) were recruited from gynecologic clinics in Baltimore, MD. Information was collected on hormonal contraceptive use, HPV genotypes, history of other sexually transmitted infections, Pap smear diagnoses, sexual behavioral and reproductive characteristics. For Aim 1: associations were assessed using prevalence ratios (PRs) with 95% confidence intervals (CIs). For Aim 2: associations between hormonal contraceptive use and incident HPV detection were measured by odds ratios (ORs) with 95% confidence intervals (CIs) estimated in generalized estimating equation models. For Aim 3: baseline pairs of cervical secretion samples matched in 5-year age groups were collected from current and non-current hormonal contraceptive users who were HPV-negative. Extracted specimens from cervical secretion samples were tested for 27 cytokines, chemokines and growth factors. Comparison of individual mean cytokine levels were made between user groups of hormonal contraceptives. Profile comparison was done using Spearman's rank correlation to determine correlations for all pairwise combinations of the cytokines, chemokines, and growth factors measured in different strata of hormonal contraceptive use and type.;Results:.;For Aim 1: more than 5 years' use of progestin-only contraceptives (POCs) was associated with 3-fold increased prevalence of any HPV [adjusted prevalence ratio (aPR): 3.16 (95% CI: 1.82-5.48)] and high-risk (HR)-HPV [aPR: 4.26 (95% CI: 1.60-11.30)] as compared to never POC users. Current POC use was positively associated with prevalence of HR-HPV (aPR: 2.44 (0.99-5.99) and any HPV (aPR: 1.58 (0.94-2.65) with the estimates bordering on statistical significance. For Aim 2: Relative to never POC users, increased incident detection of HR-HPV was observed among current users of POCs [adjusted odds ratio (aOR): 3.24 (95% CI: 1.37-7.65) after controlling for sexual behavioral factors. No similar associations were observed with the duration or recency of overall hormonal contraceptive or oral contraceptive (OC) use. For Aim 3: Compared to current users of hormonal contraceptives, significantly more positive correlations were detected among proinflammatory cytokines as well as between proinflammatory and immunoregulatory cytokines in current hormonal contraceptive users. Compared to COC users, correlation coefficients were significantly lower in magnitude among immunoregulatory cytokines such as IL9, IL15 and IL17, as well as IL5, IL15, IL17 in current POC users. Relative to non-current hormonal contraceptive users, current POC users were also found to have statistically significantly lower levels of IP10 and several immunoregulatory cytokines, including IL12, IL13, IL15.;Conclusions:.;Long-term and current use of POCs may be associated with increased risk of prevalent and incident HPV infection independent of sexual behavior among older women with normal cervical cytology. Our laboratory study showed differences in cytokine profiles between current and non-current hormonal contraceptive users as well as between current POC and COC users in HPV-negative women. These findings suggest differential impacts of exogenous hormones on cervical cytokine milieu, which in turn may potentially affect host responses to local genital infections.
机译：简介：建议长期和近期联合使用口服避孕药（COC）是宫颈癌的危险因素。由于激素避孕药使用与HPV感染之间的关联研究结果不一致，因此尚不清楚该关联是否受COC对致癌作用和/或HPV感染上游事件的影响所驱动。了解荷尔蒙避孕药使用对35岁以上女性HPV检测和宫颈免疫状况的影响，可能有助于深入了解荷尔蒙避孕药使用对宫颈癌风险的潜在生物学机制。以及宫颈细胞学检查正常的绝经女性（年龄范围：35-54岁），以调查宫颈HPV检测与激素避孕药使用之间的关联（n = 530）。这项研究有3个目的：目的1：确定激素避孕药使用与基线HPV患病率之间的关系。目的2：比较激素避孕药使用者和非使用者之间检测新HPV DNA的可能性。目的3：描述和比较激素避孕药使用者和基线时HPV阴性的非使用者的宿主宫颈细胞因子谱的差异。方法：绝经前和围绝经期妇女（年龄范围：35-54岁）从马里兰州巴尔的摩的妇科诊所招募。收集了有关激素避孕药使用，HPV基因型，其他性传播感染史，子宫颈抹片检查，性行为和生殖特征的信息。对于目标1：使用具有95％置信区间（CI）的患病率（PR）评估关联。对于目标2：荷尔蒙避孕药的使用与HPV入射检测之间的关联通过在广义估计方程模型中估计的比值比（OR）和95％置信区间（CI）进行测量。对于目标3：从HPV阴性的当前和非当前激素避孕药使用者中收集5岁年龄组匹配的基线宫颈分泌物样本。从宫颈分泌物样本中提取的标本被测试了27种细胞因子，趋化因子和生长因子。荷尔蒙避孕药使用者组之间的个体平均细胞因子水平进行了比较。使用Spearman等级相关性进行概况比较，以确定在荷尔蒙避孕药的使用和类型的不同阶层中测量的所有细胞因子，趋化因子和生长因子的成对组合的相关性；结果：。；目的1：使用5年以上仅孕激素避孕药（POC）与任何HPV的患病率增加3倍[调整的患病率（aPR）：3.16（95％CI：1.82-5.48）]和高危（HR）-HPV [aPR： 4.26（95％CI：1.60-11.30）]与从未使用POC的用户相比。当前的POC使用量与HR-HPV（aPR：2.44（0.99-5.99）和任何HPV（aPR：1.58（0.94-2.65））的患病率呈正相关，估计值具有统计学意义。对于目标2：相对于从未使用过POC的用户，在控制了性行为因素后，目前使用POC的使用者中HR-HPV的事件检出率有所提高[调整后的优势比（aOR）：3.24（95％CI：1.37-7.65）。目标3：与目前使用激素避孕药的用户相比，在当前荷尔蒙避孕药具使用者中，促炎细胞因子之间以及促炎和免疫调节细胞因子之间的正相关性明显更高。在当前的POC用户中，免疫调节细胞因子（例如IL9，IL15和IL17以及IL5，IL15，IL17）之间的相关系数在幅度上显着降低。对于非当前激素避孕药使用者，还发现当前POC使用者的IP10水平和统计学上显着较低的IP10和几种免疫调节细胞因子，包括IL12，IL13，IL15。宫颈细胞学检查正常的老年妇女中，与性行为无关的流行和事件HPV感染风险增加相关。我们的实验室研究显示，HPV阴性女性当前和非当前激素避孕药使用者之间以及当前POC和COC使用者之间的细胞因子谱存在差异。这些发现表明外源激素对宫颈细胞因子环境的不同影响，进而可能潜在地影响宿主对局部生殖器感染的反应。

著录项

  • 作者

    Soong, Thing Rinda.;

  • 作者单位

    The Johns Hopkins University.;

  • 授予单位 The Johns Hopkins University.;
  • 学科 Public health.
  • 学位 Ph.D.
  • 年度 2015
  • 页码 214 p.
  • 总页数 214
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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