HPV Splice Junction Primers for HSIL Detection
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Solution Overview
Problem
Current molecular diagnostic methods for cervical cancer screening have low Positive Predictive Value (PPV) for detecting high-grade squamous intraepithelial lesions (HSIL) due to reliance on HPV DNA tests that do not account for patterns of viral expression, leading to inadequate prediction of cancer development.
Innovation Solution
A multiplexed amplification system using Next-Generation Sequencing (NGS) technology targeting virus splice junctions to analyze the equilibrium of transcript species of high-risk HPV types, providing a snapshot of early vs. late HPV populations and correlating with lesion evolution, thereby improving diagnostic accuracy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If HPV DNA tests are used for cervical cancer screening, then sensitivity for detecting HPV infection is high, but Positive Predictive Value for detecting HSIL is low
Solution Approach 1:
The invention changes the detection parameter from HPV DNA presence to HPV RNA expression patterns (E6/E7 mRNA levels). This parameter change enables the test to distinguish between transient infections and persistent high-risk infections that lead to HSIL, thereby improving Positive Predictive Value while maintaining sensitivity
Solution Approach 2:
The invention introduces HPV RNA expression analysis as an intermediary marker between HPV DNA detection and HSIL diagnosis. By measuring E6/E7 mRNA expression levels, the test provides a more accurate prediction of cancer development potential, resolving the contradiction between high sensitivity and low PPV
2Reliability
If current molecular diagnostic methods rely on HPV genome detection, then sensitivity is high, but they do not address patterns of viral expression leading to low PPV
Solution Approach 1:
The invention extracts and analyzes specifically the E6 and E7 mRNA expression components from the total HPV viral load. By isolating and measuring these specific viral expression patterns, the test recovers the lost information about viral activity and persistence, enabling accurate HSIL prediction
Solution Approach 2:
The invention transitions from detecting total HPV DNA to specifically measuring E6/E7 mRNA expression levels. This parameter change captures the functional activity of the virus rather than just its presence, preserving critical information about viral persistence and oncogenic potential
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The method demonstrates encouraging diagnostic performance as a triage test for HSIL, offering a more accurate and cost-effective screening approach by analyzing HPV RNA expression patterns.
Implementation Method 1
A subject of the present invention is a composition of primers for detecting high grade squamous intraepithelial lesion (HSIL) comprising a first set of primers, called splice junctions set of primers
Data Source
AI summary
The present invention relates to a composition of primers for detecting HSIL comprising a first set of primers, called splice junctions set of primers which comprises at least 2 pairs of primers of each of a first subset of pairs of primers specific of HPV16, a second subset specific of HPV18, a third subset specific of HPV31, a fourth subset specific of HPV33, a fifth subset specific of HPV35, a sixth subset specific of HPV39, a seventh subset specific of HPV45, a eighth subset specific of HPV51, a ninth subset specific of HPV52, a tenth subset specific of HPV56, an eleventh subset specific of HPV58, a twelfth subset specific of HPV59 and a thirteenth subset specific of HPV66.