Geraets Daan T, van Doorn Leen-Jan, Kleter Bernhard, Colau Brigitte, Harper Diane M, Quint Wim G V
DDL Diagnostic Laboratory, Rijswijk, The Netherlands.
PLoS One. 2013 Nov 11;8(11):e80382. doi: 10.1371/journal.pone.0080382. eCollection 2013.
HPV16 variants correlate with geographic origin and ethnicity. The association between infection with a specific variant and the cervical disease risk remains unclear. We studied the prevalence, persistence and association with cervical intraepithelial neoplasia (CIN) of different HPV16 variants, using cervical swabs and whole tissue sections (WTS) of biopsies from 548 women in the placebo group of a HPV16/18 vaccine trial. In HPV16-positive samples, HPV16 variants were identified by a reverse hybridization assay (RHA). Laser-capture micro-dissection (LCM) was performed for localized detection of HPV. HPV16 variants were determined in 47 women. Frequency of mixed HPV16 variant infections was lower (8.5%) than for multiple HPV genotypes (39.1%). Among 35 women having consecutive HPV16 variant-positive swabs, 32 (91.4%) had the same variant while in three (8.6%) women a change in variant(s) was observed. HPV16-positive WTS were obtained from 12 women having consecutive HPV16 variant-positive swabs. The same variant was present in WTS of 10 women, while two were negative. WTS of five women were histologically normal. A single HPV16 variant was detected in four women having CIN1-3, while additional HPV genotypes were found in three other women having CIN2 and CIN3. In the WTS of one woman with mixed genotypes, the HPV16 variant was assigned to a CIN2 lesion by LCM. HPV16 variant infections can be effectively studied in cervical swabs and tissue specimens by the HPV16 variant RHA. Multiple HPV16 variants in one woman are rare. The HPV16 genotype consistently detected in follow-up samples usually involves a persistent infection with the same variant.
人乳头瘤病毒16型（HPV16）变体与地理起源和种族相关。特定变体感染与宫颈癌风险之间的关联仍不明确。我们利用一项HPV16/18疫苗试验安慰剂组中548名女性的宫颈拭子和活检的全组织切片（WTS），研究了不同HPV16变体的患病率、持续存在情况以及与宫颈上皮内瘤变（CIN）的关联。在HPV16阳性样本中，通过反向杂交分析（RHA）鉴定HPV16变体。进行激光捕获显微切割（LCM）以对HPV进行局部检测。在47名女性中确定了HPV16变体。混合HPV16变体感染的频率（8.5%）低于多种HPV基因型（39.1%）。在35名连续HPV16变体阳性拭子的女性中，32名（91.4%）具有相同变体，而3名（8.6%）女性观察到变体变化。从12名连续HPV16变体阳性拭子的女性中获得了HPV16阳性WTS。10名女性的WTS中存在相同变体，而2名呈阴性。5名女性的WTS组织学正常。在4名患有CIN1 - 3的女性中检测到单一HPV16变体，而在另外3名患有CIN2和CIN3的女性中发现了其他HPV基因型。在一名基因型混合的女性的WTS中，通过LCM将HPV16变体定位到一个CIN2病变。通过HPV16变体RHA可在宫颈拭子和组织标本中有效研究HPV16变体感染。一名女性中存在多种HPV16变体的情况罕见。在后续样本中持续检测到的HPV16基因型通常涉及同一变体的持续感染。
