ConVerge Diagnostic Services announces CerView E6/E7, the cutting edge technology helping to determine Pre-Cancer Progression

 HPV E6/E7 Expression: 

A Better Way to Look at Infection Progression

 Background:

Cervical cancer screening programs have been instrumental in reducing the incidence and mortality of cervical cancer.  Over the past 10 years, HPV DNA testing for high-risk sub-types has become an important adjunct to cytology (the Pap).  The combination of Pap and HPV testing used in conjunction is more effective in triaging patient follow-up care than either test as a stand-alone.

• The Pap smear has low sensitivity for high grade lesions (CIN II or greater)
• HPV DNA testing for high grade lesions has a sensitivity greater than 90% 

But….

• HPV DNA testing alone has a VERY LOW SPECIFICITY for high grade lesions
• The Positive Predictive Value (PPV) of HPV DNA for leading to a high grade lesion by biopsy is only 15-25%
• The PPV translates into unnecessary colposcopy and biopsy procedures with increased patient discomfort and overall increased healthcare costs

 Facts about the Human Papilloma Virus (HPV):

• These tiny viruses contain a small number of genes, which logically are divided into one of two “families”:
  • Early Genes:  E1, E2, E4, E5, E6, E7  and 
    • Early genes regulate production & survival of the virus in host cells
• Late Genes:  L1, L2
  • Late genes code for structural components of the viral coat
•  Most HPV infections will spontaneously resolve due to the patients’ immune response (85-90%)
• In 10-15% of patients, a persistent infection will develop.  These patients are at the greatest risk for developing invasive cancer!
• HPV DNA testing alone is NOT a specific indicator of risk for developing significant cervical neoplasia since many patients are infected, but most will clear the virus without any treatment.

 Is there a way to tell which infections will lead to significant lesions and which won’t?

 At last, the answer is - YES !!

 Introducing: CerView_E6/E7

 In MOST HPV infections, expression of the early genes (especially E6 and E7) is kept very low.  The infections which show low E6/E7 gene expression generally clear spontaneously -  including most low grade lesions (CIN I).  In persistent infections (including many high grade lesions diagnosed as CIN II or greater), molecular changes in the host cells lead to very high levels of E6/E7 gene expression. 

• The E6/E7 proteins have many ONCOGENIC properties and are important in carcinogenesis. 
• Virtually ALL invasive cervical cancers have high levels of E6/E7 expression.

Measuring E6/E7 expression thus provides MUCH GREATER SPECIFICITY and POSITIVE PREDICTIVE VALUE than HPV DNA testing alone.

• PPV is improved to 80-90%  versus the 15-25% PPV for HPV DNA testing alone
• Translation - Fewer false positive results and a reduction in unnecessary colposcopies                                                             

 How Does CerView_E6/E7 Work?

• The test is performed on material from the ThinPrep Pap vial.
• Flow cytometry and specific in situ hybridization probes are used to measure E6/E7 mRNA levels within intact cervical squamous cells.
• High levels of intracellular E6/E7 mRNA indicate that those cells are undergoing transformation to becoming cancer cells—note: it’s not possible to obtain this information when cells are lysed for PCR-based measurement methods, as in the GenProbe E6/E7 assay.

 When Should I Use the CerView_E6/E7 test?

• Negative Cytology, Positive HPV
• ASC-US Cytology, Positive HPV
• LSIL Cytology

What is the Suggested Patient Triage, with CerView_E6/E7 results?

Cytology Result	HPV Result	CerViewE6/E7	Follow-up
Negative	Screen Positive	Negative	Repeat in 1 year
Negative	Screen Positive	Positive	Repeat in 6 months
Negative	Screen Positive, 16 or 18 Positive	Negative	Repeat in 1 year
Negative	Screen Positive, 16 or 18 Positive	Positive	Colposcopy
ASC-US	Positive	Negative	Repeat in 6 months
ASC-US	Positive	Positive	Colposcopy
LSIL	-	Negative	Repeat in 6 months
LSIL	-	Positive	Colposcopy

 

References:

1. Stanley M. Pathology and Epidemiology of HPV infection in females. Gynecol Oncol 2010; 117: S5-S10.
2. Doorbar J. The Papillomavirus Life Cycle. J Clin Virol 2005; 325: S7-S15.
3. Grundhoefer D, and Patterson BK. Determination of Liquid-Based Cervical Cytology Specimen Adequacy Using Cellular Light Scatter and Flow Cytometry. Cytometry 2001; 46: 340-344.
4. Narimatsu R, and Patterson BK. High-Throughput Cervical Cancer Screening Using Intracellular Human Papillomavirus E6 and E7 mRNA Quantification by Flow Cytomtery. Am J Clin Pathol 2005; 123: 716-723.
5. Coquillard G, Palao B, and Patterson BK. Quantification of Intracellular HPV E6/E7 mRNA Expression Increases the Specificity and Positive Predictive Value of Cervical Cancer Screening Compared to HPV DNA. Gynecol Oncol 2011; 120: 89-93.