New Data Could Have Tremendous Implications For Improved Screening For Human Papillomaviruses (HPVs)

The study, the seven-year longitudinal clinical performance of the mRNA-based Aptima HPV test in a screening population in Sweden led by Professor Ola Forslund, Lund University, confirms that the Aptima HPV assay is validated with clinical efficacy up to seven years.

Human papillomaviruses (HPVs) have been shown to be causal for the development of cervical precancerous lesions and cancer². This has led to the development and wide adoption of assays with high sensitivity to detect high risk strains of HPV in cervical cancer screening programmes.^3-6 The vast majority of HPV infections are harmless and cleared naturally by the immune system, so accurate diagnosis reduces unnecessary anxiety caused by misdiagnosis⁷ and overtreatment with its associated healthcare costs⁸. Due to the large numbers involved in a screening population, even a small difference in test accuracy will have a “tremendous impact” on women being screened and healthcare costs.⁹

The accuracy of diagnosis can be improved by using mRNA assays such as the Aptima HPV assay, which target the mRNA [the activity] of the cancerous E6/E7 genes resulting in significantly greater specificity^10-14. As the presence of this mRNA indicates that the HPV virus is active, this type of assay could tremendously reduce the burden to women and to society.

The study:

• Cervical samples were frozen at -80°C [Biobank] from a population-based cohort of 95,023 women in Sweden, between May 2007 to January 2012.⁹
• Of 1,204 women that had developed cervical intraepithelial neoplasia CIN3+ after 4 months to 7 years after enrolment, baseline samples were analysed for HPV-mRNA (Aptima, Hologic) and for HPV-DNA (Cobas 4800, Roche) and results from both tests obtained for 1,172 women.⁹
• Among women ≥30 years, the longitudinal sensitivities for CIN3+ occurring 5-7 years later were comparable (76.3 % (95% CI: 65.8%- 84.3%) and 82.5% (95% CI: 72.6% -89.4%)) as were the longitudinal negative predictive values for absence of CIN3+ (99.97% (95% CI: 99.95-99.98) and 99.98% (95% CI: 99.96-99.99)), for the HPV-mRNA and HPV-DNA test.⁹
• In conclusion, HPV-mRNA testing has similar longitudinal sensitivity as HPV-DNA, implying that HPV-mRNA testing can safely be used for cervical screening.⁹

These results mean that, as countries across Europe are moving towards 3-5 year cervical cancer screening programs, laboratories can be assured that Aptima HPV assay is an effective screening tool for these programs.

Aptima HPV Assay:

The Aptima HPV Assay targets high risk HPV types that pose the largest threat to women.^2,11 DNA tests detect certain HPV genes however, cannot differentiate between the mere presence of the virus and active infection. In contrast to this, mRNA tests detect transcripts of the viral genes, which are only present if actively infected cells are present.¹⁵ While other HPV assays target DNA, the Aptima HPV Assay targets mRNA, which detects the presence and activity of high-risk HPV infection.^11,12 The Aptima HPV Assays detect the oncogenic genes E6/E7 mRNA, which is indicative of those HPV infections more likely to cause cervical disease.^10-14

References:

ICO/IARC Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases Report, 17 April 2018. http://www.hpvcentre.net/statistics/reports/XEX.pdf

Graham S., Clinical Science (2017) 131 2201–2221

Arbyn M et al., 2012. Vaccine 30(Suppl 5):F88–F99.

Dillner J. 2013. Curr Opin Obstet Gynecol 25:11–16.

Castle P et al., 2012. Vaccine 30(Suppl 5):F117–F122.

Saslow D et al,. 2012. Am J Clin Pathol 137:516–542.

McCaffery et al. Sex Transm Infect. 2006;82(2):169–74.

Sauter J et al., Acta Cytologica 2014;58:162–166

Forslund O et al., Int J Cancer. 2018 [Epub ahead of print]

Sawaya, et al. Obstet Gynecol. 2015;125(2):308-10.

Tinelli A et al., Curr Pharm Biotechnol. 2009 Dec;10(8):767-71.

Cuschieri K et al., J Med Virol. 2004 May;73(1):65-70.

Aptima HPV Assay [package insert, AW-11141-001 Rev 003 (EN)], San Diego, CA; Hologic, Inc., 2015.

Ge Y et al., Cancer Cytopathol 2017;125:652-7

Iftner et al., (GAST) J. Clin. Microbiol. 2015