单纯疱疹病毒2型作为人乳头瘤病毒的辅助因子在浸润性宫颈癌病因学中的作用

Herpes simplex virus-2 as a human papillomavirus cofactor in the etiology of invasive cervical cancer.

作者信息

Smith Jennifer S, Herrero Rolando, Bosetti Cristina, Muñoz Nubia, Bosch F Xavier, Eluf-Neto José, Castellsagué Xavier, Meijer Chris J L M, Van den Brule Adriaan J C, Franceschi Silvia, Ashley Rhoda

机构信息

Unit of Field and Intervention Studies, International Agency for Research on Cancer (IARC), Lyon, France.

出版信息

J Natl Cancer Inst. 2002 Nov 6;94(21):1604-13. doi: 10.1093/jnci/94.21.1604.

DOI:10.1093/jnci/94.21.1604

PMID:12419786

Abstract

BACKGROUND

Human papillomavirus (HPV) infection is the main cause of invasive cervical cancer, but cofactors may act in conjunction with HPV. We performed a pooled analysis of seven case-control studies to examine the effect of one possible HPV cofactor, herpes simplex virus-2 (HSV-2) infection, in the etiology of invasive cervical cancer.

METHODS

Blood and exfoliated cervical specimens were obtained from 1263 case patients with invasive cervical cancer (1158 with squamous-cell carcinomas and 105 with adeno- or adenosquamous-cell carcinomas) and 1117 age-matched control subjects. Western blot analysis and/or an enzyme-linked immunosorbent assay were used to detect type-specific serum antibodies to HSV-2 and HSV-1, and Chlamydia trachomatis serum antibodies were detected using a micro-immunofluorescence assay. HPV DNA was detected using a polymerase chain reaction assay. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were computed from unconditional logistic regression models.

RESULTS

Overall, HSV-2 seropositivity was higher among case patients with squamous-cell carcinoma (44.4%, 95% CI = 41.5% to 47.3%) or adeno- or adenosquamous-cell carcinoma (43.8%, 95% CI = 34.2% to 53.5%) than among control subjects (25.6%, 95% CI = 23.0% to 28.2%). Cervical specimens from 1098 (94.8%) squamous-cell carcinoma case patients, 95 (90.5%) adeno- or adenosquamous carcinoma case patients, and 164 (14.7%) control subjects were positive for HPV DNA. Among the HPV DNA-positive women, HSV-2 seropositivity was associated with increased risks of squamous-cell carcinoma (OR = 2.19, 95% CI = 1.41 to 3.40) and adeno- or adenosquamous-cell carcinoma (OR = 3.37, 95% CI = 1.47 to 7.74) after adjustment for potential confounders. A similar association between HSV-2 seropositivity and squamous-cell carcinoma risk was observed after further controlling for markers of sexual behavior (OR = 1.96, 95% CI = 1.24 to 3.09). Among control subjects, HSV-2 seropositivity was associated with markers of sexual behavior, but not with cervical HPV DNA positivity.

CONCLUSION

HSV-2 infection may act in conjunction with HPV infection to increase the risk of invasive cervical carcinoma.

摘要

背景

人乳头瘤病毒（HPV）感染是浸润性宫颈癌的主要病因，但辅助因素可能与HPV共同起作用。我们对7项病例对照研究进行了汇总分析，以检验一种可能的HPV辅助因素——单纯疱疹病毒2型（HSV-2）感染在浸润性宫颈癌病因学中的作用。

方法

从1263例浸润性宫颈癌病例患者（1158例鳞状细胞癌患者和105例腺或腺鳞癌患者）和1117例年龄匹配的对照者中获取血液和宫颈脱落标本。采用蛋白质印迹分析和/或酶联免疫吸附测定法检测HSV-2和HSV-1的型特异性血清抗体，采用微量免疫荧光测定法检测沙眼衣原体血清抗体。采用聚合酶链反应测定法检测HPV DNA。根据无条件逻辑回归模型计算汇总比值比（OR）和95%置信区间（CI）。

结果

总体而言，鳞状细胞癌（44.4%，95%CI=41.5%至47.3%）或腺或腺鳞癌（43.8%，95%CI=34.2%至53.5%）病例患者的HSV-2血清阳性率高于对照者（25.6%，95%CI=23.0%至28.2%）。1098例（94.8%）鳞状细胞癌病例患者、95例（90.5%）腺或腺鳞癌病例患者以及164例（14.7%）对照者的宫颈标本HPV DNA呈阳性。在HPV DNA阳性的女性中，调整潜在混杂因素后，HSV-2血清阳性与鳞状细胞癌（OR=2.19，95%CI=1.41至3.40）和腺或腺鳞癌（OR=3.37，95%CI=1.47至7.74）风险增加相关。在进一步控制性行为指标后，观察到HSV-2血清阳性与鳞状细胞癌风险之间存在类似关联（OR=1.96，95%CI=1.24至3.09）。在对照者中，HSV-2血清阳性与性行为指标相关，但与宫颈HPV DNA阳性无关。