Pérez Sonia, Cid Ana, Iñarrea Amparo, Pato Mónica, Lamas María José, Couso Bárbara, Gil Margarita, Alvarez María Jesús, Rey Sonia, López-Miragaya Isabel, Melón Santiago, Oña María de
Department of Microbiology, University Hospital of Vigo, Vigo, Spain.
Department of Microbiology, University Hospital of Ourense, Ourense, Spain.
PLoS One. 2014 Aug 11;9(8):e104678. doi: 10.1371/journal.pone.0104678. eCollection 2014.
Genetic variants of human papillomavirus types 16 and 18 (HPV16/18) could differ in their cancer risk. We studied the prevalence and association with high-grade cervical lesions of different HPV16/18 variant lineages in a case-control study including 217 cases (cervical intraepithelial neoplasia grade 2 or grade 3 or worse: CIN2 or CIN3+) and 116 controls (no CIN2 or CIN3+ in two-year follow-up). HPV lineages were determined by sequencing the long control region (LCR) and the E6 gene. Phylogenetic analysis of HPV16 confirmed that isolates clustered into previously described lineages: A (260, 87.5%), B (4, 1.3%), C (8, 2.7%), and D (25, 8.4%). Lineage D/lineage A strains were, respectively, detected in 4/82 control patients, 19/126 CIN3+ cases (OR = 3.1, 95%CI: 1.0-12.9, p = 0.04), 6/1 glandular high-grade lesions (OR = 123, 95%CI: 9.7-5713.6, p<0.0001), and 4/5 invasive lesions (OR = 16.4, 95%CI: 2.2-113.7, p = 0.002). HPV18 clustered in lineages A (32, 88.9%) and B (4, 11.1%). Lineage B/lineage A strains were respectively detected in 1/23 control patients and 2/5 CIN3+ cases (OR = 9.2, 95%CI: 0.4-565.4, p = 0.12). In conclusion, lineages A of HPV16/18 were predominant in Spain. Lineage D of HPV16 was associated with increased risk for CIN3+, glandular high-grade lesions, and invasive lesions compared with lineage A. Lineage B of HPV18 may be associated with increased risk for CIN3+ compared with lineage A, but the association was not significant. Large well-designed studies are needed before the application of HPV lineage detection in clinical settings.
人乳头瘤病毒16型和18型(HPV16/18)的基因变异体在致癌风险方面可能存在差异。在一项病例对照研究中,我们研究了不同HPV16/18变异谱系的患病率及其与高级别宫颈病变的关联,该研究纳入了217例病例(宫颈上皮内瘤变2级或3级及以上:CIN2或CIN3+)和116例对照(两年随访期间无CIN2或CIN3+)。通过对长控制区(LCR)和E6基因进行测序来确定HPV谱系。HPV16的系统发育分析证实,分离株聚为先前描述的谱系:A(260株,87.5%)、B(4株,1.3%)、C(8株,2.7%)和D(25株,8.4%)。在82例对照患者中有4例检测到D谱系/A谱系毒株,126例CIN3+病例中有19例(比值比[OR] = 3.1,95%置信区间[CI]:1.0 - 12.9,p = 0.04),1例腺性高级别病变中有6例(OR = 123,95%CI:9.7 - 5713.6,p < 0.0001),5例浸润性病变中有4例(OR = 16.4,95%CI:2.2 - 113.7,p = 0.002)。HPV18聚为A(32株,88.9%)和B(4株,11.1%)谱系。在23例对照患者中有1例检测到B谱系/A谱系毒株,5例CIN3+病例中有2例(OR = 9.2,95%CI:0.4 - 565.4,p = 0.12)。总之,HPV16/18的A谱系在西班牙占主导地位。与A谱系相比,HPV16的D谱系与CIN3+、腺性高级别病变和浸润性病变的风险增加相关。与A谱系相比,HPV18的B谱系可能与CIN3+的风险增加相关,但该关联不显著。在将HPV谱系检测应用于临床之前,需要进行大规模精心设计的研究。