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ZedScan Clinical Trials

Identification and detection of cervical disease

The ability to identify correctly those women who have and those who do not have disease is pivotal to the success of any screening programme. Prevention of cervical cancer depends on colposcopic detection and treatment of high-grade cervical intra-epithelial neoplasia (CIN 2+) in women referred with abnormal cytology.

A number of clinical studies have been completed to assess the performance of an EIS based diagnostic device in the diagnosis of cervical intraepithelial neoplasia (CIN) – Table 1.

Table 1: Clinical studies involving the use of an EIS device in the assessment of the cervix

Publication

Patients Recruited
British Journal of Obstetrics and Gynaecology, (March, 2013)* 429
Gynecological Oncology, (2009) 104
International Journal of Gynecological Cancer, (2006) 176
British Journal of Obstetrics and Gynaecology, (2005) 87
Lancet, (2000) 124

 

 

 

 

 

 

Please refer to the relevant publication for an  in-depth analysis of the data.

*Conclusion from pivotal multicentre trial:

" The use of EIS as an real-time adjunct to colposcopy improves clinical performance. The inclusion of EIS into colposcopic practice could lead to more appropriate patient management with lower intervention rates. 
 
Principal Investigators:
Prof. Henry Kitchener
Prof. Walter Prendiville
Prof. John Tidy
 

Colposcopy : Key Challenges

  •  Subjective diagnosis
    • Reliant on visual indicators of disease
    • Susceptible  to Inter and intra-operator variability
  • Inconsistent Performance
    • Reported sensitivity  for CIN2+( HG CIN) varies between 30-99%
    • Reported specificity for CIN2+ (HG-CIN) varies between 39-92%

Low colposcopic performance can result in failure to detect disease (inadequate sensitivity) or unnecessary treatment in the absence of disease (inadequate specificity).

Zilico’s multi-centre clinical trial (BJOG, 2013) has successfully demonstrated that ZedScan, when used as an adjunct to colposcopy, addresses these key challenges to deliver improvements in diagnostic accuracy.

 

HPV Testing as a Primary Screen

The superior sensitivity of molecular HPV testing (90%) relative to cytology (50%) is a significant driver for its consideration as a primary screening tool.

  • Several studies have indicated that HPV testing is effective at finding disease within the screening population and can reduce the incidence of cervical cancer by increasing the detection and treatment of precancerous lesions missed by cytology
  • The predictive value of a negative test is much higher than that for cytology, providing increased confidence that disease is unlikely to develop before the subsequent round of screening and the interval between screening tests could be extended
     
  • However, HPV DNA is a marker of infection rather than disease and most infections will resolve without progression to high-grade CIN that requires treatment 
     
  • As a result the specificity of the HPV test for detection of current disease is low (50-75%) which means that the predictive value of the test is also low (17-29%)

A transition to HPV testing as the primary screen would alter the characteristics of the population referred to colposcopy.

  • Although the referred population would include almost all the women at risk of developing high-grade CIN, the low specificity means that there would also be a large number of women who have an HPV infection without disease
  • As a consequence  the total number of patients referred to colposcopy will increase with a higher rate of false positives due to the lower specificity of HPV testing


The increased number of women referred to colposcopy, many of whom would present with new infections which are likely to clear within 5 years, will create challenges for existing patient management strategies.

A further consideration is that, whilst HPV testing would pick up women with early stage pre-cancerous lesions, this may not translate to improvements in colposcopic performance.
Porras et al 1 reported  that colposcopy was poor at detecting cases of CIN2+ in HPV positive women  with no acetowhite lesions  present;  they concluded:

 “the major concern with switching from cytology to more sensitive HPV screening is management of the many HPV-positive women, including those with still nonvisible ≥CIN2 lesions. Our data support the need for a nonvisual diagnostic method to guide management and treatment of HPV-positive women.”

EIS is a non-optical diagnostic method for the diagnosis of high grade CIN, providing clinicians with increased confidence when deciding how to manage the patient, at first visit. 

1Porras et al, (2012) " Switch from cytology-based to human papillomavirus test-based cervical screening: implications for colposcopy", Int. J Cancer, 130, 1879-1887

 

Performance of ZedScan as an adjunct to colposcopy

  •  Increased Sensitivity
    • Ability to detect more patients with high grade CIN
  • Increased Specificity
    • Reduction in false positives
  • Higher PPV
    • Increased confidence to treat patients with disease at first visit (See & Treat/Select & Treat)

ROC curve showing improved performance with ZedScan