Hall Michaela T, Simms Kate T, Lew Jie-Bin, Smith Megan A, Saville Marion, Canfell Karen
Cancer Research Division, Cancer Council NSW, Sydney, Australia.
School of Public Health, University of Sydney, Sydney, Australia.
PLoS One. 2018 Feb 14;13(2):e0185332. doi: 10.1371/journal.pone.0185332. eCollection 2018.
Many countries are transitioning from cytology-based to longer-interval HPV screening. Trials comparing HPV-based screening to cytology report an increase in CIN2/3 detection at the first screen, and longer-term reductions in CIN3+; however, population level year-to-year transitional impacts are poorly understood. We undertook a comprehensive evaluation of switching to longer-interval primary HPV screening in the context of HPV vaccination. We used Australia as an example setting, since Australia will make this transition in December 2017.
Using a model of HPV vaccination, transmission, natural history and cervical screening, Policy1-Cervix, we simulated the planned transition from recommending cytology every two years for sexually-active women aged 18-20 to 69, to recommending HPV screening every five years for women aged 25-74 years. We estimated rates of CIN2/3, cervical cancer incidence, and mortality for each year from 2005 to 2035, considering ranges for HPV test accuracy and screening compliance in the context of HPV vaccination (current coverage ~82% in females; ~76% in males).
Transient increases are predicted to occur in rates of CIN2/3 detection and invasive cervical cancer in the first two to three years following the screening transition (of 16-24% and 11-14% in respectively, compared to 2017 rates). However, by 2035, CIN2/3 and invasive cervical cancer rates are predicted to fall by 40-44% and 42-51%, respectively, compared to 2017 rates. Cervical cancer mortality rates are predicted to remain unchanged until ~2020, then decline by 34-45% by 2035. Over the period 2018-2035, switching to primary HPV screening in Australia is expected to avert 2,006 cases of invasive cervical cancer and save 587 lives.
Transient increases in detected CIN2/3 and invasive cancer, which may be detectable at the population level, are predicted following a change to primary HPV screening. This is due to improved test sensitivity bringing forward diagnoses, resulting in longer term reductions in both cervical cancer incidence and mortality. Fluctuations in health outcomes due to the transition to a longer screening interval are predicted to occur for 10-15 years, but cervical cancer rates will be significantly reduced thereafter due to the impact of HPV vaccination and HPV screening. In order to maintain confidence in primary HPV screening through the transitional phase, it is important to widely communicate that an initial increase in CIN2/3 and perhaps even invasive cervical cancer is expected after a national transition to primary HPV screening, that this phenomenon is due to increased prevalent disease detection, and that this effect represents a marker of screening success.
许多国家正从基于细胞学的筛查转向间隔时间更长的人乳头瘤病毒(HPV)筛查。比较基于HPV的筛查与细胞学筛查的试验报告称,首次筛查时CIN2/3(宫颈上皮内瘤变2/3级)的检出率有所增加,且CIN3+(宫颈上皮内瘤变3级及以上)的长期检出率有所下降;然而,人们对人群层面逐年的过渡影响了解甚少。我们在HPV疫苗接种的背景下,对转向间隔时间更长的初次HPV筛查进行了全面评估。我们以澳大利亚为例,因为澳大利亚将于2017年12月进行这一转变。
我们使用一个关于HPV疫苗接种、传播、自然史和宫颈筛查的模型Policy1-Cervix,模拟了计划中的转变,即从建议18至20岁至69岁的性活跃女性每两年进行一次细胞学筛查,转变为建议25至74岁的女性每五年进行一次HPV筛查。我们估计了2005年至2035年每年的CIN2/3发生率、宫颈癌发病率和死亡率,同时考虑了HPV检测准确性和筛查依从性在HPV疫苗接种背景下的范围(目前女性接种覆盖率约为82%;男性约为76%)。
预计在筛查转变后的头两到三年,CIN2/3的检出率和浸润性宫颈癌的发病率将出现短暂上升(分别比2017年的发生率高出16 - 24%和11 - 14%)。然而,到2035年,预计CIN2/3和浸润性宫颈癌的发生率将分别比2017年的发生率下降40 - 44%和42 - 51%。预计宫颈癌死亡率在2020年左右之前将保持不变,到2035年将下降34 - 45%。在2018年至2035年期间,澳大利亚转向初次HPV筛查预计可避免2006例浸润性宫颈癌病例,并挽救587条生命。
预计转向初次HPV筛查后,在人群层面可能会检测到CIN2/3和浸润性癌症的短暂增加。这是由于检测灵敏度提高导致诊断提前,从而使宫颈癌发病率和死亡率长期下降。预计向更长筛查间隔转变导致的健康结果波动将持续10至15年,但此后由于HPV疫苗接种和HPV筛查的影响,宫颈癌发生率将显著降低。为了在过渡阶段保持对初次HPV筛查的信心,重要的是要广泛宣传,在全国转向初次HPV筛查后,预计CIN2/3甚至浸润性宫颈癌会初步增加,这种现象是由于普遍疾病检测增加所致,且这种效应是筛查成功的标志。