ISPO, Florence, Italy.
Cancer Epidemiol Biomarkers Prev. 2010 Sep;19(9):2389-400. doi: 10.1158/1055-9965.EPI-10-0131.
The aim of this multicentric study was to identify human papillomavirus (HPV) type distribution in invasive cervical cancer and high-grade cervical intraepithelial neoplasia 2/3 (CIN2/3) in Italy.
Cases were sampled through the electronic databases at the pathology units of eight centers in six regions from central and southern Italy. HPV types were detected from paraffin-embedded tissue samples and cervical specimens through amplification of HPV DNA with GP5+/GP6+ primers, followed by genotyping with reverse line blot (RLB). Untyped HPV-positive samples were sequenced. HPV-negative samples underwent nested PCR, followed by either RLB or sequencing. Finally, the remaining HPV-negative samples were amplified with primers targeting the virus E6 to E7 regions.
From 1,162 cases initially selected, 722 samples were further analyzed: 144 CIN2, 385 CIN3, 157 invasive squamous carcinomas, and 36 adenocarcinomas. Samples (6.9%) were HPV negative. The proportion of HPV16/18 was 60.8%, 76.6%, and 78.8% in CIN2, CIN3, and invasive cancers, respectively (P trend = 0.004). There was a significant decreasing trend of HPV16/18 with age in invasive cancers, going from 92% in women <35 years to 73% in women >55 years (P = 0.036). The proportion of coinfections was 16.8%, 15.5%, and 10.0% in CIN2, CIN3, and invasive cancers, respectively (P trend = 0.07).
The proportion of invasive cancers caused by HPV16/18 decreases with age at diagnosis.
The absolute risk of an invasive cancer due to non-HPV16/18 in women under 35 is extremely low. This finding might prompt us to rise the age at which public HPV screening for vaccinated women should start.
本多中心研究的目的是在意大利确定人乳头瘤病毒(HPV)在浸润性宫颈癌和高级别宫颈上皮内瘤变 2/3(CIN2/3)中的分布类型。
通过意大利中部和南部六个地区的八个中心的病理科电子数据库采集病例。通过 GP5+/GP6+引物扩增 HPV DNA,对石蜡包埋组织和宫颈标本进行 HPV 类型检测,然后进行反向线杂交(RLB)基因分型。未分型的 HPV 阳性样本进行测序。HPV 阴性样本进行巢式 PCR,然后进行 RLB 或测序。最后,用针对病毒 E6 至 E7 区的引物扩增其余 HPV 阴性样本。
从最初选择的 1162 例中,进一步分析了 722 例样本:144 例 CIN2,385 例 CIN3,157 例浸润性鳞状细胞癌和 36 例腺癌。(6.9%)样本 HPV 阴性。CIN2、CIN3 和浸润性癌中 HPV16/18 的比例分别为 60.8%、76.6%和 78.8%(P 趋势=0.004)。在浸润性癌中,HPV16/18 随年龄的增加而显著降低,从<35 岁女性的 92%降至>55 岁女性的 73%(P=0.036)。CIN2、CIN3 和浸润性癌中合并感染的比例分别为 16.8%、15.5%和 10.0%(P 趋势=0.07)。
HPV16/18 引起的浸润性癌的比例随诊断时的年龄而降低。
<35 岁女性由于非 HPV16/18 引起的浸润性癌的绝对风险极低。这一发现可能促使我们提高已接种疫苗女性开始公共 HPV 筛查的年龄。