Dalstein Véronique, Riethmuller Didier, Prétet Jean-Luc, Le Bail Carval Karine, Sautière Jean-Loup, Carbillet Jean-Pierre, Kantelip Bernadette, Schaal Jean-Patrick, Mougin Christiane
Laboratoire de Biologie Cellulaire et Moléculaire, Institut d'Etude et de Transfert de Gènes, Centre Hospitalier Universitaire, Hopital Jean Minjoz, Bld. Fleming, 25030 Besançon cedex, France.
Int J Cancer. 2003 Sep 1;106(3):396-403. doi: 10.1002/ijc.11222.
Oncogenic HPV types are the major cause of worldwide cervical cancer, but only a small proportion of infected women will develop high-grade cervical intraepithelial neoplasia or cancer (CIN2/3+). We performed a prospective study including 781 women with normal, atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LGSIL) cytology, and infected or not by high-risk (HR) HPV tested by Hybrid Capture II. Women were followed up every 6 months for a median period of 22 months. Among the HR-HPV-positive women at entry, more than half cleared their virus in 7.5 months; the clearance rate was greater for low viral loads than for high loads and also was higher in women with an initial ASCUS/LGSIL smear than in women with normal cytology. The incidence of cytologic abnormalities strongly depended on baseline viral load and HR-HPV persistence. Maintenance of cytologic abnormalities was associated with the outcome of HR-HPV status (negative<transient<persistent) but not with baseline load. Progression to CIN2/3+ was achieved only in women with persistent HR-HPV infection. The risk of CIN2/3+ also was increased with initial high loads (> or =100 pg/mL). Conversely, women who were consistently HR-HPV negative or transiently HR-HPV positive, whatever the cytology at baseline was, did not develop CIN2/3+ during follow-up. Age seemed to affect only the rate of incident HR-HPV infection. In conclusion, our data suggest that women repeatedly tested positive for HR-HPV are at risk of developing CIN2/3+, even when initial cytology is normal. A high viral load could be used as a short-term marker of progression toward precancerous lesions, although lower load does not inevitably exclude progressive disease.
致癌性人乳头瘤病毒（HPV）类型是全球宫颈癌的主要病因，但只有一小部分感染HPV的女性会发展为高级别宫颈上皮内瘤变或癌症（CIN2/3+）。我们开展了一项前瞻性研究，纳入了781名细胞学检查结果为正常、意义不明确的非典型鳞状细胞（ASCUS）或低级别鳞状上皮内病变（LGSIL）的女性，她们通过第二代杂交捕获法检测是否感染高危（HR）HPV。每6个月对这些女性进行一次随访，中位随访期为22个月。在入组时HR-HPV阳性的女性中，超过一半在7.5个月内清除了病毒；低病毒载量女性的清除率高于高病毒载量女性，初始涂片为ASCUS/LGSIL的女性清除率也高于细胞学检查正常的女性。细胞学异常的发生率强烈依赖于基线病毒载量和HR-HPV的持续存在情况。细胞学异常的持续存在与HR-HPV状态的结果（阴性<短暂阳性<持续阳性）相关，但与基线病毒载量无关。只有持续感染HR-HPV的女性才会进展为CIN2/3+。初始高病毒载量（≥100 pg/mL）时CIN2/3+的风险也会增加。相反，无论基线细胞学检查结果如何，持续HR-HPV阴性或短暂HR-HPV阳性的女性在随访期间均未发生CIN2/3+。年龄似乎仅影响HR-HPV感染的发生率。总之，我们的数据表明，即使初始细胞学检查正常，多次检测HR-HPV呈阳性的女性仍有发生CIN2/3+的风险。高病毒载量可作为癌前病变进展的短期标志物，尽管低病毒载量并不能必然排除疾病进展。
