Rate of cervical cancer, severe intraepithelial neoplasia, and adenocarcinoma in situ in primary HPV DNA screening with cytology triage: randomised study within organised screening programme

Abstract

Objective To assess the performance and impact of primary human papillomavirus (HPV) DNA screening with cytology triage compared with conventional cytology on cervical cancer and severe pre-cancerous lesions. Design Randomised trial. Setting Population based screening programme for cervical cancer in southern Finland in 2003-5. Participants 58 076 women, aged 30-60, invited to the routine population based screening programme for cervical cancer. Interventions Primary HPV DNA test (hybrid capture II) with cytology triage if the result was positive or conventional cytological screening (reference). Main outcome measures Rate of cervical cancer, cervical intraepithelial neoplasia (CIN) grade III, and adenocarcinoma in situ (as a composite outcome referred to as CIN III+) during 2003-7 through record linkage between files from the screening registry and the national cancer registry. Results In the HPV and conventional arms there were 95 600 and 95 700 woman years of follow-up and 76 and 53 cases of CIN III+, respectively (of which six and eight were cervical cancers). The relative rate of CIN III+ in the HPV arm versus the conventional arm was 1.44 (95% confidence interval 1.01 to 2.05) among all women invited for screening and 1.77 (1.16 to 2.74) among those who attended. Among women with a normal or negative test result, the relative rate of subsequent CIN III+ was 0.28 (0.04 to 1.17). The rate of cervical cancer between arms was 0.75 (0.25 to 2.16) among women invited for screening and 1.98 (0.52 to 9.38) among those who attended. Conclusions When incorporated into a well established organised screening programme, primary HPV screening with cytology triage was more sensitive than conventional cytology in detecting CIN III+ lesions. The number of cases of cervical cancer was small, but considering the high probability of progression of CIN III the findings are of importance regarding cancer prevention.Trial registration Current Controlled Trials ISRCTN23885553.

The HPV test has similar sensitivity but more overdiagnosis than the Pap test—A randomised health services study on cervical cancer screening in Finland

“…7,8,12 The negative predictive value of the test on invasive cancer should be distinguished from the negative predictive value on CIN3. The former is related to sensitivity, the latter to both sensitivity and overdiagnosis.…”

“…[1][2][3][4][5] The few follow-up studies have focused on pre-invasive lesions and on the length of reassurance that a negative test provides. [6][7][8][9][10] Only few studies have had emphasis on public health aspects. 11,12 The purpose of screening is to prevent invasive cervical cancer and the demonstration of this effect requires follow-up for incident invasive cancers after the screen.…”

Human Telomerase Gene and High-Risk Human Papillomavirus Infection are Related to Cervical Intraepithelial Neoplasia

“…Cervical cancer has become a global health problem, the use of HR-HPV DNA tests in primary screening have been shown in several studies to be more sensitive than conventional cytology in detecting cervical cancer and severe precancerous lesions and may serve to prolong the screening interval (Anttila et al, 2010). But the specificities of HR-HPV DNA tests for identification of cervical neoplasia are lower than those for cytology, especially among younger women (Szarewski et al, 2008).…”

“…Slides were prepared using a liquid-based cytology method, the ThinPrep system (Cytyc Corporation, MA, USA). Cytological classifications of disease grade were made in conformity to Bethesda2001 criteria (Anttila et al, 2010). A diagnosis was assigned to each case as having negative for intraepithelial lesion or malignancy (NILM) or having an epithelial cell abnormality such as atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma (SCC) and atypical glandular cells (AGC) (Solomon et al, 2002).…”

Cervical cancer patterns with automation‐assisted and conventional cytological screening: A randomized study

“…[4][5][6]8,17,18 When assessed in the randomized screening setting in the Finnish cervical cancer screening programme, the sensitivity for CIN3þ is higher for HPV screening than for conventional cytological screening. 17 Specificity of HPV-DNA test is very similar to conventional cytological Pap-smear test among women aged 35 years or older; but among younger women the low specificity of the HPV test is still a problem. 19 In the first published studies and trials on new methods for cervical cancer screening, the research environment can be very different from the routine setting.…”