Triage of high-risk HPV positive women in cervical cancer screening

Abstract

Current knowledge on morphological biomarkers, molecular biomarkers and combined triage strategies will be discussed to give an overview of the state-of-the-art on triaging hrHPV positive women. The literature search was limited to studies on triage strategies for hrHPV positive women. Expert commentary: Experience with morphology-based biomarkers makes these a valuable triage method. However, they lack the ability of differentiating productive from transforming infections. Molecular biomarkers are objective, highly reproducible, can be used in high throughput testing, and show promising results. With more extensive knowledge on these molecular markers, cervical cancer screening may transform to a full molecular screening in the future.

DNA methylation markers as a triage test for identification of cervical lesions in a high risk human papillomavirus positive screening cohort

“…In addition to our methylation markers, other methylation markers have been reported to be noninferior to cytology as well . The limitations of cytology as a triage test are: (i) inherent subjective nature of the test, (ii) inability of high‐throughput testing, (iii) high level of skills required for cytotechnicians, (iv) moderate specificity (weighted mean ~60% (range 49.6–76.8%)) despite its high sensitivity (weighted mean 80%), (v) time consuming preparation of the cytological slides and (vi) inability of cytology to be performed on self‐collected samples . Same limitations account for triage tests based on immunostaining such as p16/KI67 .…”

“…The limitations of cytology as a triage test are: (i) inherent subjective nature of the test, (ii) inability of high‐throughput testing, (iii) high level of skills required for cytotechnicians, (iv) moderate specificity (weighted mean ~60% (range 49.6–76.8%)) despite its high sensitivity (weighted mean 80%), (v) time consuming preparation of the cytological slides and (vi) inability of cytology to be performed on self‐collected samples . Same limitations account for triage tests based on immunostaining such as p16/KI67 . A full molecular triage alternative is expected to alleviate these issues and further improve cervical cancer screening programs .…”

“…Beside cytology and methylation analysis, hrHPV partial genotyping has also been proposed as a triage test for hrHPV positive women, with HPV16/18 typing already implemented in the USA referral guidelines . However, sensitivity and specificity of HPV16/18 triage is ~60% and 80% to detect CIN2+ lesions, which makes it inferior compared to our methylation markers panels. In our study, despite the small number of samples, combining HPV genotyping with the methylation marker panels the sensitivity minimally increased, but was, as expected, accompanied with a decrease in specificity, resulting in no overall additive effect by combining HPV16/18 genotyping with our methylation marker panels.…”

Presence of koilocytosis in low‐grade smears of high‐risk HPV‐positive women is a negative predictor for cervical intraepithelial neoplasia grade 3 or more

“…To improve the limited specificity of hrHPV testing an additional triage test is needed. Cytological reflex‐triage testing is the first test of choice as this has been shown to be an effective tool …”

“…Cytological reflex-triage testing is the first test of choice as this has been shown to be an effective tool. 4 The Netherlands is one of the first countries worldwide to implement organised primary hrHPV screening in 2017 for women aged 30-60 years with a 5-year screening interval. However, women aged 40-50 years testing negative for the presence of hrHPV are allowed to be retested after 10 years.…”