Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, P.O. Box 281, S-171 77 Stockholm, Sweden.
Cancer Epidemiol Biomarkers Prev. 2013 Jan;22(1):150-8. doi: 10.1158/1055-9965.EPI-12-0953-T. Epub 2012 Nov 15.
A strong association has been shown between high viral DNA load (VL) of human papillomavirus (HPV) type 16 and risk for cervical cancer in situ (CIS). However, little data is available for the significance of VL in invasive squamous cell carcinoma (SCC).
In 2 nested case-control studies among women participating in cervical screening, with a cytologically normal first smear, we collected 5,665 smears from 621 women with CIS, 457 with SCC, and individually matched controls. All smears were tested for HPV, and VLs of HPV16 positive smears were quantified using real time-PCR. The median follow-up until diagnosis of CIS or SCC was 6.1 to 7.7 years.
Low VL's were common among both CIS and SCC case women, until 1 to 2 years before diagnosis when a surge in VL occurred. The relative risk (RR) associated with low viral load of HPV16 was around 10 for CIS, and 10 to 20 for SCC throughout 10 years before diagnosis, compared with HPV16-negative women. For women with medium to high VL, the risk for CIS was greatly increased from 5 years before diagnosis [RR, 19; 95% confidence interval (CI), 7-48]. In SCC, a high VL conferred an increased risk, but only from 3 years before diagnosis [RR, 60; 95% CI, 6-580].
We show differing risk functions associated with HPV16 viral load in CIS and SCC, respectively. We further show that viral loads were unexpectedly low early in the SCC disease process.
HPV16 viral load appears highly complex which may limit its use in cervical screening.
已有研究表明，人乳头瘤病毒（HPV）16 型病毒载量（VL）高与宫颈原位癌（CIS）的风险之间存在很强的关联。然而，关于 HPV16 VL 在浸润性鳞状细胞癌（SCC）中的意义的数据较少。
在参与宫颈筛查的女性中进行了 2 项巢式病例对照研究，这些女性的首次细胞学涂片正常，我们从 621 例 CIS 患者、457 例 SCC 患者和个体匹配的对照者中收集了 5665 份涂片。所有涂片均进行 HPV 检测，并使用实时 PCR 定量 HPV16 阳性涂片的 VL。中位随访时间为诊断 CIS 或 SCC 前 6.1 至 7.7 年。
CIS 和 SCC 病例女性的低 VL 很常见，直到诊断前 1 至 2 年 VL 才激增。与 HPV16 阴性女性相比，HPV16 低载量与 CIS 的相对风险（RR）约为 10，与 SCC 的 RR 为 10 至 20，在诊断前 10 年一直如此。对于中高 VL 的女性，从诊断前 5 年开始，CIS 的风险大大增加[RR，19；95%置信区间（CI），7-48]。在 SCC 中，高 VL 也会增加风险，但仅从诊断前 3 年开始[RR，60；95%CI，6-580]。
我们分别展示了 HPV16 VL 与 CIS 和 SCC 相关的不同风险函数。我们还进一步表明，在 SCC 疾病过程的早期，病毒载量出人意料地低。
HPV16 病毒载量似乎非常复杂，这可能限制了其在宫颈筛查中的应用。
