Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México D.F. 14080, Mexico.
Unidad de Epidemiología Clínica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán INCMNSZ, México D.F. 14000, Mexico.
Gynecol Oncol. 2014 Sep;134(3):534-9. doi: 10.1016/j.ygyno.2014.06.018. Epub 2014 Jun 27.
The molecular and epidemiologic effect of human papillomavirus (HPV) coinfections in the risk of developing cervical cancer is yet unclear. The aim of this study was to determine the frequency HPV coinfections at different stages of cervical lesions in the development of cervical cancer and the impact of HPV specific type interactions on high-grade squamous intraepithelial lesions (HSIL) and invasive cervical cancer (ICC) risk.
HPV testing was performed in 931 cervical samples diagnosed as: negative for intraepithelial lesion or malignancy (NILM); low-grade squamous intraepithelial lesion (LSIL); HSIL; and ICC. For HPV detection and typing two sets of primers from the L1 region were used in the polymerase chain reaction method (PCR) (MY09/MY11/HMB01 and L1C1/L1C2.1/L1C2.2) and HPV type was determined by PCR product sequence. To look for multiple HPV infections, the E6 nested multiplex PCR method was performed in all DNA samples. Odds ratios were calculated as indexes of the strength of the association between the sample category (LSIL/NILM or ICC/HSIL) and the presence of a given viral combination.
In HPV positive samples, coinfections are as common in ICC/HSIL as in LSIL/NILM (47.12% and 40.17%, respectively). There is an increased risk to ICC/HSIL when multiple high-risk HPV types are present. The coinfection of HPV68 with HPV16 increases the risk of ICC/HSIL (OR=14.54, P=0.012, after multivariate adjustment), related to the presence of HPV16 or HPV68 alone.
These results sustain that specific HPV coinfections confer an increased risk to develop ICC/HSIL.
人乳头瘤病毒（HPV）合并感染对宫颈癌发病风险的分子流行病学影响尚不清楚。本研究旨在探讨不同宫颈病变阶段 HPV 合并感染的频率，以及 HPV 特定型别间相互作用对高级别鳞状上皮内病变（HSIL）和浸润性宫颈癌（ICC）风险的影响。
对 931 例经组织学诊断为：宫颈上皮内瘤变或恶性病变阴性（NILM）、低级别鳞状上皮内病变（LSIL）、HSIL 和 ICC 的宫颈样本进行 HPV 检测。采用聚合酶链反应（PCR）法（MY09/MY11/HMB01 和 L1C1/L1C2.1/L1C2.2），应用两套来自 L1 区的引物进行 HPV 检测和分型，通过 PCR 产物测序确定 HPV 型别。对所有 DNA 样本进行 E6 巢式多重 PCR 法检测，以寻找多重 HPV 感染。采用比值比（OR）作为样本分类（LSIL/NILM 或 ICC/HSIL）与特定病毒组合存在之间关联强度的指标。
在 HPV 阳性样本中，ICC/HSIL 中合并感染与 LSIL/NILM 中合并感染一样常见（分别为 47.12%和 40.17%）。当存在多种高危型 HPV 时，ICC/HSIL 的发病风险增加。HPV68 与 HPV16 的合并感染增加了 ICC/HSIL 的发病风险（OR=14.54，P=0.012，经多变量校正后），这与 HPV16 或 HPV68 单独存在有关。
这些结果表明，特定的 HPV 合并感染增加了发展为 ICC/HSIL 的风险。
