可能致癌的 HPV 亚型是 HSIL 的病因，也是 HPV 临床检测阴性的原因——一项欧洲前瞻性单中心研究。
Possibly carcinogenic HPV subtypes are a cause of HSIL and negative clinical HPV tests - A European prospective single center study.
机构信息
Department of Obstetrics & Gynecology, Medical University of Graz, Austria.
Diagnostic and Research Institute of Pathology, Medical University of Graz, Austria.
出版信息
Gynecol Oncol. 2020 Jul;158(1):112-116. doi: 10.1016/j.ygyno.2020.04.685. Epub 2020 Apr 27.
OBJECTIVE
To correlate p16 positive cervical precancers of 388 consecutive patients from a single European center with the preceding clinical HPV-DNA and HPV E6/E7 mRNA screening test.
METHOD
374/388 patients had a HSIL (CIN 2/3) and 14/388 AIS (6 pure and 8 combined AIS/HSIL). Lesional tissues of HSIL/AIS with negative Cobas and/or Aptima HPV tests underwent HPV genotyping with CHIPRON HPV 3.5 LCD-array. Selected cases were subjected to a cancer hot spot analysis.
RESULTS
The Aptima test missed 10/388 (2.6%) and the Cobas test seven of 388 (1.8%) precancers associated HPV-HR. Both HPV tests were negative in 20/374 precancers (5.3%; 17 HSIL/CIN3, two HSIL/CIN2, one AIS). Due to insufficient DNA four of 20 double negative cases (three HSIL, one AIS) were not genotyped. In the remaining cases, two of 20 (10%) HSIL genotyping detected HR-HPV subtypes. 10/20 (50%) HSIL were associated with possibly carcinogenic and low risk HPV (four x HPV73, three x HPV 53, one x HPV 82, one x HPV 67 and one x HPV 6), all of which are not included in both HPV tests. Two of 20 (10%) HSIL were negative with all HPV tests; one of these HSIL had a somatic PIK3CA gene mutation and the other had a single nucleotide variant in the APC gene. Three of 20 HSIL (15%) were thin HSIL (≤9 cell layers thick).
CONCLUSIONS
Possibly carcinogenic HPV subtypes not included in the clinical HPV tests may account for the small gap of missed HSIL in clinical HPV screening. True HPV negative HSIL are exceedingly rare. Expanding HPV testing to include more possibly carcinogenic HPV subtypes may further reduce cervical cancer.
目的
将来自欧洲单一中心的 388 例连续患者的 p16 阳性宫颈前癌与之前的临床 HPV-DNA 和 HPV E6/E7 mRNA 筛查试验相关联。
方法
374/388 例患者为 HSIL（CIN 2/3），14/388 例为 AIS（6 例纯 AIS/HSIL 和 8 例混合 AIS/HSIL）。HSIL/AIS 病变组织的 Cobas 和/或 Aptima HPV 检测呈阴性，采用 CHIPRON HPV 3.5 LCD-array 进行 HPV 基因分型。选择部分病例进行癌症热点分析。
结果
Aptima 检测漏诊了 388 例中的 10 例（2.6%）和 Cobas 检测漏诊了 388 例中的 7 例（1.8%）与 HPV-HR 相关的前癌。20/374 例前癌（5.3%；17 例 HSIL/CIN3、2 例 HSIL/CIN2、1 例 AIS）的两种 HPV 检测均为阴性。由于 DNA 不足，20 例双阴性病例中的 4 例（3 例 HSIL、1 例 AIS）未进行基因分型。在剩余的病例中，20 例中的 2 例（10%）HSIL 基因分型检测到 HR-HPV 亚型。20 例 HSIL 中有 10/20（50%）与可能致癌和低危 HPV 相关（4 例 x HPV73、3 例 x HPV 53、1 例 x HPV 82、1 例 x HPV 67 和 1 例 x HPV 6），这两种 HPV 均未包含在两种 HPV 检测中。20 例 HSIL 中有 2 例（10%）与两种 HPV 检测均为阴性；其中 1 例 HSIL 存在 PIK3CA 基因突变，另 1 例存在 APC 基因突变。20 例 HSIL 中有 3 例（15%）为薄型 HSIL（≤9 层细胞厚）。
结论
未包含在临床 HPV 检测中的可能致癌 HPV 亚型可能是导致临床 HPV 筛查中 HSIL 漏诊的小差距的原因。真正的 HPV 阴性 HSIL 极为罕见。扩大 HPV 检测以包含更多可能致癌的 HPV 亚型可能会进一步降低宫颈癌的发生率。
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