Role of E6/E7 mRNA test in the diagnostic algorithm of HPV-positive patients showing ASCUS and LSIL: clinical and economic implications in a publicly financed healthcare system

Abstract

Objective: Colposcopy is widely used to triage women with mild cervical abnormalities. However, this approach is associated with low specificity and predictive value. The efficacy of E6/E7 mRNA test for this purpose has been demonstrated, but studies estimating its cost-effectiveness are still lacking. Given the limited healthcare financial resources, such an evaluation is a priority. Methods: We analyzed the clinical history of 432 women referred to colposcopy and colposcopy-directed biopsy for persisting ASCUS and LSIL, and compared three alternative triage protocols: immediate colposcopy; reflex HPV DNA testing and HPV DNA plus mRNA tests in sequence. Results: Molecular tests in sequence significantly reduce colposcopy referral, cost for assessed women, and cost for CIN2 detected. On the other hand, incremental cost-effectiveness ratio of this protocol was the highest. Conclusion: Our preliminary data, providing an estimation of the economic burden deriving from the introduction of E6/E7 mRNA test in the triage algorithm of patients with mild cervical abnormalities, may be useful for future healthcare policy.

Keywords:

• ASCUS and LSIL
• cost–effectiveness analysis
• E6/E7 HPV-mRNA test
• human papillomavirus
• ICER
• persistent HPV infections
• triage test

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Persistent infection with oncogenic human papillomavirus is a key factor that could drive cervical intraepithelial lesions to progress toward invasive cancer.

• Atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion cytologic categories have a low positive predictive value for CIN2+.

• Human papillomavirus-DNA test demonstrated low specificity and poor positive predictive value.

• mRNA test would better identify infections at high risk of persistence.

• mRNA test demonstrated high clinical performance.

• The introduction of mRNA test raises concern regarding how to best manage women with borderline or minor cytologic abnormalities.

• It would be of great importance to economically evaluate the possible introduction of mRNA test in the triage of patients with atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion.

• The addition of mRNA test to diagnostic work-up presently in use would lead to clinical and economic advantages.

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