Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors:: Implications for screening and prevention
Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors:: Implications for screening and prevention
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DOI：
10.1093/jnci/djj067
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发表时间：
2006-03-01
影响因子：
10.3
通讯作者：
Bosch, FX
中科院分区：
文献类型：
--
作者：
Castellsagué, X;Díaz, M;Bosch, FX
背景：大多数子宫颈肿瘤为鳞状细胞癌。虽然此类子宫颈癌的发病率随着时间的推移而下降，但近年来子宫颈腺癌的发病率却有所上升。人乳头瘤病毒（HPV）感染及其辅助因子在多大程度上可以解释这种差异趋势尚不清楚。方法：我们汇集了来自三大洲的八项宫颈癌病例对照研究的数据。167例宫颈浸润性腺癌患者（腺癌112例，腺鳞癌55例）和1881例医院对照。采用GP5+/6+通用引物系统对宫颈标本中的HPV DNA进行分析，并对33种HPV基因型进行特异性杂交。对血样进行衣原体和单纯疱疹病毒2 （HSV-2）血清学分析。采用多变量无条件逻辑回归模型计算95%置信区间（ci）的比值比（ORs）。所有具有统计学显著性的检验均为双侧检验。结果：与hpv阴性妇女相比，hpv阳性妇女宫颈癌的调整后总优势比为81.3 （95% CI = 42.0至157.1）。HPV 16和HPV 18是病例患者和对照组中最常检测到的两种HPV类型。这两种类型出现在82%的患者中。总体上和hpv阳性妇女中显示与宫颈腺癌有统计学显著正相关的辅助因素包括从未上学、卫生不良、性行为相关变量、长期使用激素避孕、高胎次和HSV-2血清阳性。胎次与腺癌的相关性较弱，且仅在hpv阳性的女性中存在。使用宫内节育器（IUD）与腺癌风险呈统计学显著负相关（曾经使用过宫内节育器与从未使用过，OR = 0.41 [95% CI = 0.18 ~ 0.93]）。吸烟和衣原体血清阳性与疾病无关。结论：HPV是宫颈腺癌的关键危险因素。在初级筛查中使用目前混合的HPV型别进行HPV检测，并接种针对主要HPV型别的HPV疫苗，应能减少全世界这种癌症的发病率。
Background: Most cancers of the uterine cervix are squamous cell carcinomas. Although the incidence of such carcinomas of the uterine cervix has declined over time, that of cervical adenocarcinoma has risen in recent years. The extent to which human papillomavirus (HPV) infection and cofactors may explain this differential trend is unclear. Methods: We pooled data from eight case-control studies of cervical cancer that were conducted oil three continents. A total of 167 case patients with invasive cervical adenocarcinoma (112 with adenocarcinoma and 55 with adenosquamous carcinoma) and 1881 hospital-based control subjects were included. HPV DNA was analyzed in cervical specimens with the GP5+/6+ general primer system followed by type-specific hybridization for 33 HPV genotypes. Blood samples were analyzed for chlamydial and herpes simplex virus 2 (HSV-2) serology. Multivariable unconditional logistic regression modeling was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). All tests of statistical significance were two-sided. Results: The adjusted overall odds ratio for cervical adenocarcinoma in HPV-positive women compared with HPV-negative women was 81.3 (95% CI = 42.0 to 157.1). HPV 16 and HPV 18 were the two most commonly detected HPV types in case patients and control subjects. These two types were present in 82% of the patients. Cofactors that showed clear statistically significant positive associations with cervical adenocarcinoma overall and among HPV-positive women included never schooling, poor hygiene, sexual behavior-related variables, long-term use of hormonal contraception, high parity, and HSV-2 seropositivity. Parity had a,weaker association with adenocarcinoma and only among HPV-positive women. Use of an intrauterine device (IUD) had a statistically significant inverse association with risk of adenocarcinoma (for ever use of an IUD compared with never use, OR = .41 [95% CI = 0.18 to 0.93]). Smoking and chlamydial seropositivity were not associated with disease. Conclusions: HPV appears to be the key risk factor I. or cervical adenocarcinoma. HPV testing in primary screening using current mixtures of HPV types and HPV vaccination against main HPV types should reduce the incidence of this cancer worldwide.