Science & Technology

Why Pap test needs improvement

Over a 100 million women are screened for cervical cancer each year in the Western World and through these programs cervical cancer was reduced by 50%, but the system lacks efficiency, automation and objectivity.

Traditional cervical cancer screening (cytology or Pap smear or Pap test named after Doctor Georgios Papanikolaou who invented it) was introduced several decades ago and has not changed much since. Cells scraped from the cervix are fixed on a glass slide and checked for physical signs indicative of malignant transformations (pre-cancer or cancer).

The evaluation is ultimately performed by highly experienced professionals; and patients are managed according to very complex algorithms.

This system is subjective, intricate, only moderately sensitive for the disease and cannot identify “at-risk individuals”.

In the early 80s Professor Harald zur Hausen discovered that a virus, called the Human papillomavirus causes the large majority of cervical cancers. Today we are preparing for the HPV test, which detects the presence of the virus in the cervical sample, to take over the place of the Pap smear in screening.

It is a big step forward HPV testing being very sensitive (approx. 95% versus 50%), highly objective and finding almost all at risk women. However, it creates a new problem to solve: specificity. HPV has a specificity of approx. 90% – inadequate for the cost-efficiency requirements of screening. Only about 10% of the women infected with the virus develop dysplasia which has to be treated. The question is how to find these women: how to “triage” them. The obvious answer to this question is to bring back the Pap smear as a reflex test in lack of anything better. But because of the low sensitivity of Pap smear many repeat tests called follow-ups will be required and the complexity will not disappear either.

The scientific community has been for long looking for adequate answers for this question, and numerous attempts at developing a triage test are known: HPV RNA, HPV typing, immunostaining, mRNA marker panels, methylation marker panels, HPV methylation testing etc.

We believe the CONFIDENCE™ Marker stands out from this crowd due to having the following qualities:

  • it is a single host gene methylation marker
  • offering automated PCR setup and automated result evaluation
  • with very high sensitivity and high specificity
  • capable of assessing the risk of an underlying CIN2+ condition even if no visible signs of the cervical disease can be found.

A prospective study has been conducted since mid-2013 with outpatients clinics and colposcopy clinics in Hungary enrolling over 6,000 women to assess the performance of the CONFIDENCE™ tests. The study produced very promising results.