Xi Long Fu, Schiffman Mark, Koutsky Laura A, Hughes James P, Winer Rachel L, Mao Constance, Hulbert Ayaka, Lee Shu-Kuang, Shen Zhenping, Kiviat Nancy B
Department of Pathology (LFX, AH, ZS, NBK) and Department of Obstetrics and Gynecology (CM), School of Medicine, and Department of Epidemiology (LFX, LAK, RLW, SKL) and Department of Biostatistics (JPH), School of Public Health and Community Medicine, University of Washington, Seattle, WA; Division of Cancer Epidemiology and Genetics (MS), National Cancer Institute, Bethesda, MD.
J Natl Cancer Inst. 2014 Sep 13;106(10). doi: 10.1093/jnci/dju270. Print 2014 Oct.
Data on clinical outcomes of infection with variants of oncogenic human papillomavirus (HPV) types other than HPV16 and HPV18 are rare. We investigated intratypic variations in non-HPV16/18 oncogenic types and their corresponding relationships with cervical intraepithelial neoplasia grades 2-3 (CIN2/3).
Study subjects were women who were positive for one or more of 11 non-HPV16/18 oncogenic types. Subjects were followed every six months for two years for detection of HPV and cervical lesions. Variant lineages were defined by sequencing the 3' part of the long control region and the entire E6/E7 region of HPV genome. Lineage-associated risk of CIN2/3 was assessed using logistic regression with generalized estimating equations.
A total of 4591 type-specific HPV infections among 2667 women were included in the analysis. The increase in risk of CIN2/3 was statistically significant for women with HPV31 A or B compared with C variants, HPV33 A1 compared with B variants, HPV45 A3 or B2 compared with B1 variants, HPV56 B compared with A2 variants, and HPV58 A1 or A3 compared with C variants. For these five types, the adjusted odds ratio associated with CIN2/3 was 2.0 (95% confidence interval [CI] = 1.5 to 2.6) for infections with single-type high-risk (HR) variants, 1.7 (95% CI = 1.0 to 2.7) for infections with two or more types but only one HR variant, and 5.3 (95% CI = 3.1 to 8.4) for infections with HR variants of two or more types as compared with those with single-type non-HR variants. The likelihood of CIN2/3 was similar for women with HPV16 infection and for those with HPV58 A1 variant infection.
These findings suggest that for a given HPV type, intratypic nucleotide changes may alter phenotypic traits that affect the probability of neoplasia.
关于致癌性人乳头瘤病毒（HPV）16型和18型以外其他HPV类型感染的临床结局数据很少。我们研究了非HPV16/18致癌型的型内变异及其与宫颈上皮内瘤变2 - 3级（CIN2/3）的对应关系。
研究对象为感染11种非HPV16/18致癌型中一种或多种的女性。对研究对象每6个月随访一次，持续两年，以检测HPV和宫颈病变。通过对HPV基因组的长控制区3'部分和整个E6/E7区进行测序来定义变异谱系。使用广义估计方程的逻辑回归评估与CIN2/3相关的谱系风险。
分析纳入了2667名女性中的4591种型特异性HPV感染。与C变异体相比，HPV31 A或B型感染的女性发生CIN2/3的风险增加具有统计学意义；与B变异体相比，HPV33 A1型感染的女性发生CIN2/3的风险增加具有统计学意义；与B1变异体相比，HPV45 A3或B2型感染的女性发生CIN2/3的风险增加具有统计学意义；与A2变异体相比，HPV56 B型感染的女性发生CIN2/3的风险增加具有统计学意义；与C变异体相比，HPV58 A1或A3型感染的女性发生CIN2/3的风险增加具有统计学意义。对于这五种类型，与CIN2/3相关的调整后比值比在单型高危（HR）变异体感染时为2.0（95%置信区间[CI] = 1.5至2.6），在感染两种或更多类型但仅一种HR变异体时为1.7（95% CI = 1.0至2.7），在感染两种或更多类型的HR变异体时为5.3（95% CI = 3.1至8.4），而单型非HR变异体感染的女性发生CIN2/3的可能性与之相似。HPV16感染的女性和HPV58 A1变异体感染的女性发生CIN2/3的可能性相似。
这些发现表明，对于特定的HPV类型，型内核苷酸变化可能会改变影响瘤变概率的表型特征。
