Xi Long Fu, Koutsky Laura A, Castle Philip E, Wheeler Cosette M, Galloway Denise A, Mao Constance, Ho Jesse, Kiviat Nancy B
Department of Pathology, School of Medicine, University of Washington, 1914 North 34th St, Suite 300, Seattle, WA 98103, USA.
J Natl Cancer Inst. 2009 Feb 4;101(3):153-61. doi: 10.1093/jnci/djn461. Epub 2009 Jan 27.
The clinical relevance of the amount of human papillomavirus type 18 (HPV18) DNA in cervical tissue (ie, HPV18 DNA load) is unknown.
Study subjects were 303 women who were HPV18 positive at enrollment into the Atypical Squamous Cells of Undetermined Significance (ASC-US) and Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study. HPV18 DNA load, expressed as copies of HPV18 per nanogram of cellular DNA, at enrollment was quantitatively measured. Subjects were followed up semiannually for a period of 2 years for detection of cervical intraepithelial neoplasia 2-3 (CIN2-3). A linear regression model was used to examine associations of CIN2-3 with HPV18 DNA load. All statistical tests were two-sided.
CIN2-3 was confirmed in 92 of 303 (30.4%) HPV18-positive women. Among women without CIN2-3, HPV18 DNA load was positively associated with increasing severity of cervical cytology at enrollment (Ptrend < .001). However, among those with CIN2-3, HPV18 DNA load was not associated with severity of cervical cytology at enrollment (Ptrend = .33). The ratios of geometric means of HPV18 DNA load at enrollment among women with CIN2-3, relative to those without, were 6.06 (95% confidence interval [CI] = 0.31 to 117.92) for those with normal cytology at enrollment, 0.50 (95% CI = 0.10 to 2.44) for those with ASC-US, 0.11 (95% CI = 0.03 to 0.46) for those with LSIL, and 0.07 (95% CI = 0.01 to 0.80) for those with high-grade squamous intraepithelial lesion (HSIL). After adjusting for age and coinfection with other high-risk HPVs, a statistically significant association of lower HPV18 DNA load with CIN2-3 was observed among women with LSIL or HSIL at enrollment (P = .02). Within the 2-year period, HPV18 DNA load was unrelated to the timing of CIN2-3 diagnosis. Overall results were similar when the outcome was CIN3.
HPV18 DNA load was higher for women with LSIL or HSIL at enrollment with no evidence of CIN2-3 during the 2-year follow-up period than it was for women with CIN2-3. Thus, testing for high levels of HPV18 DNA does not appear to be clinically useful.
宫颈组织中18型人乳头瘤病毒（HPV18）DNA的含量（即HPV18 DNA载量）的临床相关性尚不清楚。
研究对象为303名在非典型鳞状细胞意义不明确（ASC-US）和低级别鳞状上皮内病变（LSIL）分流研究入组时HPV18呈阳性的女性。定量测量入组时以每纳克细胞DNA中HPV18的拷贝数表示的HPV18 DNA载量。对受试者进行为期2年的每半年一次的随访，以检测宫颈上皮内瘤变2-3级（CIN2-3）。使用线性回归模型来检验CIN2-3与HPV18 DNA载量之间的关联。所有统计检验均为双侧检验。
303名HPV18阳性女性中有92名（30.4%）确诊为CIN2-3。在无CIN2-3的女性中，HPV18 DNA载量与入组时宫颈细胞学严重程度的增加呈正相关（趋势P<0.001）。然而，在患有CIN2-3的女性中，HPV18 DNA载量与入组时宫颈细胞学严重程度无关（趋势P=0.33）。CIN2-3女性入组时HPV18 DNA载量的几何平均数与无CIN2-3女性的几何平均数之比，入组时细胞学正常的女性为6.06（95%置信区间[CI]=0.31至117.92），ASC-US的女性为0.50（95%CI=0.10至2.44），LSIL的女性为0.11（95%CI=0.03至0.46），高级别鳞状上皮内病变（HSIL）的女性为0.07（95%CI=0.01至0.80）。在调整年龄和与其他高危HPV的合并感染后，在入组时患有LSIL或HSIL的女性中观察到较低的HPV18 DNA载量与CIN2-3之间存在统计学上的显著关联（P=0.02）。在2年期间内，HPV18 DNA载量与CIN2-3诊断时间无关。当结局为CIN3时，总体结果相似。
入组时患有LSIL或HSIL且在2年随访期内无CIN2-3证据的女性的HPV18 DNA载量高于患有CIN2-3的女性。因此，检测高水平的HPV18 DNA似乎在临床上并无用处。
