Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
J Natl Cancer Inst. 2011 May 4;103(9):737-43. doi: 10.1093/jnci/djr061. Epub 2011 Apr 11.
Human papillomavirus (HPV) infection of the genital mucosa is thought to require trauma to the cervicovaginal epithelium. Therefore, we determined whether a cytology specimen collection procedure (Pap smear), which disrupts the epithelium by design, renders the cervix more susceptible to HPV infection in a primate model.
In a series of female rhesus macaques, a speculum examination was performed with (n = 8) or without (n = 4) a cytology specimen collection procedure as it is commonly practiced in a gynecology clinic. An internal digital examination was performed after specimen collection using Surgilube (n = 4) or 1% iota-carrageenan, a previously indentified HPV inhibitor (n = 4) as the lubricant. The cervix was then inoculated with HPV16 pseudovirions expressing red fluorescent protein. After 3 days, the reproductive tracts were excised and the cervix was cryosectioned. Sections were analyzed by fluorescent confocal microscopy for the number of red fluorescent protein-positive keratinocytes.
Substantial infection of the ectocervix, the transformation zone, and the endocervix was detected, but only in conjunction with the cytology specimen collection procedure (cytology using Surgilube vs without cytology using Surgilube, mean = 84 infectious events per section vs mean = 0.05 infectious events per section, difference = 84 infectious events per section, 95% confidence interval = 19 to 384 infectious events per section). When the carrageenan gel was substituted for Surgilube for an internal digital examination, the mean number of infectious events decreased (carrageenan gel vs Surgilube, mean = 3.5 events per section vs mean = 84 infectious events per section difference = 81 events per section, 95% confidence interval = 33 to 213 events per section).
These findings indicate that cytology screening in women might lead to a transient enhancement of susceptibility to HPV infection and that use of a carrageenan-based gel during the examination might mitigate this enhancement.
人们认为，人乳头瘤病毒（HPV）感染生殖器黏膜需要创伤宫颈阴道上皮。因此，我们在灵长类动物模型中确定了一种细胞学标本采集程序（巴氏涂片）是否会通过设计破坏上皮，从而使宫颈更容易感染 HPV。
在一系列雌性恒河猴中，按照妇科诊所的常规方法进行阴道镜检查（n=8）或不进行细胞学标本采集程序（n=4）。在标本采集后，使用 Surgilube（n=4）或以前鉴定为 HPV 抑制剂的 1%iota-卡拉胶（n=4）作为润滑剂进行内部数字检查。然后将 HPV16 假病毒颗粒表达的红色荧光蛋白接种到宫颈上。3 天后，切除生殖道并对宫颈进行冷冻切片。通过荧光共聚焦显微镜分析红色荧光蛋白阳性角质形成细胞的数量。
在外阴、转化区和宫颈内均检测到大量感染，但仅与细胞学标本采集程序（使用 Surgilube 的细胞学检查与不使用 Surgilube 的细胞学检查相比，每节平均=84 个感染事件与每节平均=0.05 个感染事件，差异=84 个感染事件，95%置信区间=19 至 384 个感染事件）相关。当内部数字检查用卡拉胶凝胶代替 Surgilube 时，感染事件的平均数量减少（卡拉胶凝胶与 Surgilube 相比，平均=每节 3.5 个事件与平均=84 个感染事件，差异=每节 81 个事件，95%置信区间=33 至 213 个事件）。
这些发现表明，女性的细胞学筛查可能导致 HPV 感染易感性短暂增强，而在检查过程中使用基于卡拉胶的凝胶可能会减轻这种增强。
