Reliable triage methods are key

Extended genotyping and liquid-based cytology take cervical cancer screening triage to the next level.^1-4

In the HPV primary screening approach, when the HPV test result is positive, a triage test can be performed in order to inform the appropriate patient management strategy. The result of the triage test helps determine whether the patient needs a colposcopy with biopsy, a treatment or a simple follow-up evaluation at a specified timeframe.⁵

There are multiple triage strategies possible after a positive HPV test, including HPV genotyping, cytology testing, visual inspection with acetic acid (VIA) or colposcopy.⁵ 

HPV genotyping – and more so extended genotyping – provides information on the immediate and future risk of cervical precancer of a woman and can be integrated in the initial HPV test.^1,2,5

Liquid-based cytology uses a standardised sample collection that significantly enhances specimen quality and detection of cervical lesions.^3,4 In addition, it can be performed on the same sample as the initial HPV test.

Extended genotyping is advancing HPV testing and enhancing clinical management by providing specific, actionable insights to assist in reducing patient call-backs and unnecessary colposcopies.¹

There are 12 high-risk HPV genotypes identified as oncogenic:
HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59.⁶

Yet, HPV genotypes vary in prevalence, but also in their potential to cause cervical lesions.^1,2,6

HPV 16 and 18 are responsible for about 74% of all cervical cancer cases in Europe and have been targeted by vaccination since 2006.^6,7

But not all HPV tests are equivalent. By identifying which HPV genotype is present, HPV extended genotyping can stratify the risk of CIN3+ to help guide clinical decision.^1,8 In this aspect, cytology and partial genotyping provide restrained information for the evaluation of true clinical risk.⁸

The concept of grouping HPV genotypes into clusters may ease the implementation of HPV testing information into screening algorithms as it simplifies the clinical management.^1,8,11
 

What differentiated patient management could look like in the future*¹²

Liquid-based cytology has revolutionised Pap screening by significantly enhancing specimen quality and detection of cervical lesions and reducing patient call-backs while improving cost-effectiveness.^3,4

Cervical cancer incidence and mortality has declined by 70% since the introduction of Pap screening in developed countries with well-established screening programmes, and in which women are screened at regular intervals.¹⁵

However, not all Pap tests are the same. Conventional Pap testing comes with many limitations that may lead to inaccuracies and equivocal diagnoses.¹⁶

Comparison of conventional and liquid-based cytology.^3,4

Principle	Conventional Pap test Brush contents are smeared directly onto the slide	Liquid-based cytology (LBC) The cells from the brush are deposited into liquid preservative which is then used to make a slide A cell enrichment process can be performed to further improve the quality of the slide
Standardised sample collection	Variability in sample collection
Slide preparation	Manual	Automated
Little to no obscuring material
Easy slide evaluation
Reduced screening time
Performance	Frequent unsatisfactory reports	Improved specimen adequacy Reduced unsatisfactory reports Increased disease detection
Additional testing	Not always possible	Allows for additional molecular testing – such as HPV testing – and immunocytochemistry from the same sample Compatible with co- and reflex testing

* Hypothetical patient management algorithm, adapted from the proposed new screening algorithm for the national cervical cancer prevention programme in Sweden.^12
† Depending on age and other factors, some low-oncogenic hrHPV genotypes might not require cytology testing.^12
‡ Depending on age and other clinical parameters.¹²

ASC-US, atypical squamous cells of undetermined significance; CIN3+, cervical intraepithelial neoplasia grade 3 or higher; FDA, Food and Drug Administration; hr, high-risk; HPV, human papillomavirus; LBC, liquid-based cytology; Pap, Papanicolaou.

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