HPV16/18 型血清阳性的流行病学研究及其与 HPV16、-18 型感染后风险的关系。
Epidemiological study of anti-HPV16/18 seropositivity and subsequent risk of HPV16 and -18 infections.
机构信息
Division of Cancer Epidemiology and Genetics, Infections and Immunoepidemiology Branch, National Cancer Institute, National Institutes of Health, 6120 Executive Blvd, Ste 550, Rockville, MD 20852, USA.
出版信息
J Natl Cancer Inst. 2010 Nov 3;102(21):1653-62. doi: 10.1093/jnci/djq384. Epub 2010 Oct 13.
BACKGROUND
Infection with human papillomavirus (HPV) 16 or HPV18 elicits an antibody response, but whether the elicited antibodies protect women against subsequent infection by a homologous HPV type compared with seronegative women is unknown.
METHODS
Study participants were women aged 18-25 years at enrollment in the control group of the ongoing National Cancer Institute-sponsored, community-based, randomized HPV16/18 Costa Rica Vaccine Trial. At enrollment, 2813 participants were negative for cervical HPV16 DNA and 2950 for HPV18 DNA. Women were interviewed regarding sociodemographic data and medical and health history. Medical and pelvic examinations were conducted for all consenting sexually experienced women. Serum samples taken at enrollment were tested for total HPV16/18 antibodies with a polyclonal enzyme-linked immunosorbent assay, and cervical specimens were tested for type-specific HPV DNA over 4 years of follow-up. Using Poisson regression, we compared rate ratios of newly detected cervical HPV16 or HPV18 infection among homologous HPV-seropositive and HPV-seronegative women, adjusting for age, education, marital status, lifetime number of sexual partners, and smoking.
RESULTS
There were 231 newly detected HPV16 infections during 5886 person-years among HPV16-seronegative women compared with 12 newly detected HPV16 infections during 581 person-years among HPV16-seropositive women with the highest HPV16 sero-levels. There were 136 newly detected HPV18 infections during 6352 person-years among HPV18-seronegative women compared with six new infections detected during 675 person-years among HPV18 seropositives with the highest sero-levels. After controlling for risk factors associated with newly detected HPV infection, having high HPV16 antibody titer at enrollment was associated with a reduced risk of subsequent HPV16 infection (women in the highest tertile of HPV16 antibody titers, adjusted rate ratio = 0.50, 95% confidence interval = 0.26 to 0.86 vs HPV16-seronegative women). Similarly, having high HPV18 antibody titer at enrollment was associated with a reduced risk of subsequent HPV18 infection (women in the highest tertile of HPV18 antibody titers, adjusted rate ratio = 0.36, 95% confidence interval = 0.14 to 0.76 vs HPV18-seronegative women).
CONCLUSION
In this study population, having high antibody levels against HPV16 and HPV18 following natural infection was associated with reduced risk of subsequent HPV16 and HPV18 infections.
背景
人乳头瘤病毒（HPV）16 或 HPV18 的感染会引发抗体反应，但与血清阴性女性相比，所引发的抗体是否能保护女性免受同源 HPV 型别的后续感染尚不清楚。
方法
本研究的参与者为参加正在进行的美国国立癌症研究所（NCI）赞助的、基于社区的、随机 HPV16/18 哥斯达黎加疫苗试验的对照组中年龄在 18-25 岁的女性。在入组时，2813 名参与者的宫颈 HPV16 DNA 检测为阴性，2950 名参与者的 HPV18 DNA 检测为阴性。对所有同意进行性经验的女性进行社会人口统计学数据、医疗和健康史的访谈。对所有同意的有性经验的女性进行医学和盆腔检查。在入组时采集的血清样本用多克隆酶联免疫吸附试验检测 HPV16/18 抗体总水平，在 4 年的随访期间，采集宫颈标本检测 HPV16/18 型特异性 DNA。采用泊松回归，我们比较了 HPV16 血清学阳性和 HPV16 血清学阴性女性中同源 HPV16 或 HPV18 新感染的发病率比值，同时调整了年龄、教育程度、婚姻状况、终生性伴侣数和吸烟状况。
结果
在 HPV16 血清学阴性女性中，5886 人年中有 231 例新发现的 HPV16 感染，而在 HPV16 血清学阳性女性中，581 人年中有 12 例新发现的 HPV16 感染，这些 HPV16 血清学阳性女性的 HPV16 血清学水平最高。在 HPV18 血清学阴性女性中，6352 人年中有 136 例新发现的 HPV18 感染，而在 HPV18 血清学阳性女性中，675 人年中有 6 例新发现的 HPV18 感染，这些 HPV18 血清学阳性女性的 HPV18 血清学水平最高。在控制与新发现 HPV 感染相关的危险因素后，入组时高 HPV16 抗体滴度与随后 HPV16 感染风险降低相关（HPV16 抗体滴度最高三分位组，调整后的发病率比=0.50，95%置信区间=0.26 至 0.86 与 HPV16 血清学阴性女性相比）。同样，入组时高 HPV18 抗体滴度与随后 HPV18 感染风险降低相关（HPV18 抗体滴度最高三分位组，调整后的发病率比=0.36，95%置信区间=0.14 至 0.76 与 HPV18 血清学阴性女性相比）。
结论
在本研究人群中，自然感染 HPV16 和 HPV18 后产生高抗体水平与随后 HPV16 和 HPV18 感染的风险降低有关。
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