Berumen J, Ordoñez R M, Lazcano E, Salmeron J, Galvan S C, Estrada R A, Yunes E, Garcia-Carranca A, Gonzalez-Lira G, Madrigal-de la Campa A
Laboratorio Multidisciplinario de Investigación, Escuela Militar de Graduados de Sanidad y Escuela Médico Militar, Universidad del Ejército y Fuerza Aérea, México D.F.
J Natl Cancer Inst. 2001 Sep 5;93(17):1325-30. doi: 10.1093/jnci/93.17.1325.
Human papillomavirus 16 (HPV16) has a number of variants, each with a different geographic distribution and some that are associated more often with invasive neoplasias. We investigated whether the high incidence of cervical cancer in Mexico (50 cases per 100 000 women) may be associated with a high prevalence of oncogenic HPV16 variants.
Cervical samples were collected from 181 case patients with cervical cancer and from 181 age-matched control subjects, all from Mexico City. HPV16 was detected with an E6/E7 gene-specific polymerase chain reaction, and variant HPV classes and subclasses were identified by sequencing regions of the E6 and L1/MY genes. Clinical data and data on tumor characteristics were also collected. All statistical tests were two-sided.
HPV16 was detected in cervical scrapes from 50.8% (92 of 181) of case patients and from 11% (20 of 181) of control subjects. All HPV16-positive samples, except one, contained European (E) or Asian-American (AA) variants. AA and E variants were found statistically significantly more often in case patients (AA = 23.2% [42 of 181]; E = 27.1% [49 of 181]) than in control subjects (AA = 1.1% [two of 181]; E = 10% [18 of 181]) (P<.001 for case versus control subjects for either E or AA variants, chi2 test). However, the frequency of AA variants was 21 times higher in cancer patients than in control subjects, whereas that ratio for E variants was only 2.7 (P =.006, chi2 test). The odds ratio (OR) for cervical cancer associated with AA variants (OR = 27.0; 95% confidence interval [CI] = 6.4 to 113.7) was higher than that associated with E variants (OR = 3.4; 95% CI = 1.9 to 6.0). AA-positive case patients (46.2 +/- 12.5 years [mean +/- standard deviation]) were 7.7 years younger than E-positive case patients (53.9 +/- 12.2 years) (P =.004, Student's t test). AA variants were associated with squamous cell carcinomas and adenocarcinomas, but E variants were associated with only squamous cell carcinomas (P =.014, Fisher's exact test).
The high frequency of HPV16 AA variants, which appear to be more oncogenic than E variants, might contribute to the high incidence of cervical cancer in Mexico.
人乳头瘤病毒16型（HPV16）有多种变体，每种变体的地理分布不同，有些变体更常与浸润性肿瘤相关。我们调查了墨西哥宫颈癌的高发病率（每10万名女性中有50例）是否可能与致癌性HPV16变体的高流行率有关。
从墨西哥城的181例宫颈癌患者和181例年龄匹配的对照者中采集宫颈样本。用E6/E7基因特异性聚合酶链反应检测HPV16，并通过对E6和L1/MY基因区域进行测序来鉴定HPV变体类别和亚类。还收集了临床数据和肿瘤特征数据。所有统计检验均为双侧检验。
在50.8%（181例中的92例）的病例患者宫颈刮片中检测到HPV16，在11%（181例中的20例）的对照者中检测到。除一份样本外，所有HPV16阳性样本均含有欧洲（E）或亚美（AA）变体。在病例患者中发现AA和E变体的比例在统计学上显著高于对照者（AA = 23.2% [181例中的42例]；E = 27.1% [181例中的49例]），而对照者中AA = 1.1% [181例中的2例]；E = 10% [181例中的18例]）（E或AA变体的病例与对照者比较，P<0.001，卡方检验）。然而，癌症患者中AA变体的频率比对照者高21倍，而E变体的该比例仅为2.7（P = 0.006，卡方检验）。与AA变体相关的宫颈癌优势比（OR）（OR = 27.0；95%置信区间[CI] = 6.4至113.7）高于与E变体相关的优势比（OR = 3.4；95%CI = 1.9至6.0）。AA阳性的病例患者（46.2±12.5岁[平均值±标准差]）比E阳性的病例患者（53.9±12.2岁）年轻7.7岁（P = 0.004，Student t检验）。AA变体与鳞状细胞癌和腺癌相关，但E变体仅与鳞状细胞癌相关（P = 0.014，Fisher精确检验）。
HPV16 AA变体的高频率似乎比E变体更具致癌性，这可能是墨西哥宫颈癌高发病率的原因之一。
