Screening women for cervical cancer carcinoma with a HPV mRNA test: first results from the Venice pilot program

Abstract

Background:HPV DNA-based screening is more effective than a Pap test in preventing cervical cancer, but the test is less specific. New HPV tests have been proposed for primary screening. The HPV mRNA test showed a similar or slightly lower sensitivity than the HPV DNA tests but with a higher specificity. We report the results of an organised HPV mRNA-based screening pilot program in Venice, Italy.Methods:From October 2011 to May 2014, women aged 25–64 years were invited to undergo a HPV mRNA test (Aptima). Those testing positive underwent cytological triage. Women with positive cytology were referred to colposcopy, whereas those with negative cytology were referred to repeat the HPV mRNA test 1 year later. The results of the HPV mRNA test program were compared with both the local historical cytology-based program and with four neighbouring DNA HPV-based pilot projects.Results:Overall, 23 211 women underwent a HPV mRNA test. The age-standardised positivity rate was 7.0%, higher than in HPV DNA programs (6.8% relative rate (RR) 1.11, 95% confidence interval (CI) 1.05–1.17). The total colposcopy referral was 5.1%, double than with cytology (2.6% RR 2.02, 95% CI 1.82–2.25) but similar to the HPV DNA programs (4.8% RR 1.02; 95% CI 0.96–1.08). The cervical intraepithelial neoplasia grade 2+ detection rate with HPV mRNA was greater than in the HPV DNA programs at baseline (RR 1.50; 95% CI 1.19–1.88) and not significantly lower at the 1-year repeat (RR 0.70; 95% CI 0.40–1.16). The overall RR was 1.29 (95% CI 1.05–1.59), which was much higher than with cytology (detection rate 5.5‰ vs 2.1‰ RR 2.50, 95% CI 1.76–3.62).Conclusions:A screening programme based on the HPV mRNA obtained results similar to those observed with the HPV DNA test. In routine screening programmes, even a limited increase in HPV prevalence may conceal the advantage represented by the higher specificity of HPV mRNA.

Determinants of Viral Oncogene E6-E7 mRNA Overexpression in a Population-Based Large Sample of Women Infected by High-Risk Human Papillomavirus Types

“…When we applied this value to the whole screened population, and with the assumption that HPV mRNA-positive HPV DNA-negative women are a small proportion of the screened population, ranging from 0.6% to 1.5% (7,(9)(10)(11), the positivity rate would be about 5.5 to 6.5%. Our data are consistent with those reported in other studies, ranging from 57% to 85% in HPV DNA-positive women (7,(9)(10)(11)(12) and from 4.7% to 10% in the general population (8)(9)(10)(11)(12)(13).…”

“…The tests targeting HPV E6-E7 mRNA have been suggested both as a putative primary screening test (7,8) and as a triage test instead of cytology (9).…”

Risk of CIN2 or more severe lesions after negative HPV‐mRNA E6/E7 overexpression assay and after negative HPV‐DNA test: Concurrent cohorts with a 5‐year follow‐up

“…Therefore, we cannot exclude that differences in terms of underlying risk of infection, previous screening, prevalence of CIN lesions could exist between the two populations, Furthermore, the histological endpoints were not assessed by the same labs and differences in the evaluation of CIN may have occurred . In fact, we previously showed that the results at first screening were quite similar as regards HPV positivity and detection of CIN2+, notwithstanding some different process indicators, such as positivity at cytology triage, which was performed by different laboratories. Nevertheless, since the present study regarded the results at rescreening of women that were negative at previous screening round, the differences in previous screening uptake have been minimized.…”

“…The projects' protocols have been previously described. 18,23 In Venice, cervical cells were collected in a Thin-Prep transport device (Hologic, San Diego, CA) suitable for both tests, while two separate samples (a conventional smear for cytological triage and a sample in Qiagen Standard Transport Medium, Qiagen, Hilden, Germany) were obtained within the HPV-DNA-based projects.…”

<p>Clinical Performance of Human Papillomavirus (HPV) Testing versus Cytology for Cervical Cancer Screening: Results of a Large Danish Implementation Study</p>

“…[11][12][13][14][15][16][17] On this basis, data on the performance of HPV-based screening in a real-world clinical setting, in contrast to a randomised research setting, are beginning to emerge. 12,15,[18][19][20][21][22][23][24][25][26][27][28] However, only few of these studies compared HPV-based screening with a contemporary control group screened by cytology. 12,18,19 In Denmark, national guidelines recommend screening every 3 years in women aged 23-49 and every 5 years in women aged 50-64.…”