HPV Primary Cervical Screening: Making the Switch from Cytology to HPV testing
Cervical screening has employed the Papanicolaou (Pap) test for over 80 years to detect cervical pre-cancer and cancer in women. The Pap test can be considered one of the most effective disease prevention strategies, preventing countless cases and mortalities associated with cervical cancer. However, it has its limitations, even with modern improvements such as liquid based cytology, sampling, sensitivity and screening subjectivity has reported up to a 40% false negative rate globally. The Human Papillomavirus (HPV) has long been known to be the primary aetiological factor in
the pathogenesis of cervical cancer and there are 14 known high-risk HPV subtypes [16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68]. Of these HPV 16 and 18 are associated with ~70% of all cervical cancer cases.
HPV testing has been used with great success in Ireland to triage low-grade cytology screening results since 2015. It has also been used as a test of cure following treatment and in the management of uncertainty at colposcopy since 2012 and 2014. More recently, using HPV rather than Cytology as the primary screening test has been shown in numerous international randomised control trials to have a significantly higher sensitivity and negative predictive value and based on this evidence, organised screening programmes worldwide are making the switch to HPV primary screening.
Following the HIQA “Heath technology assessment of HPV testing as the primary screening method for cervical screening” in 2017, The Irish Cervical Screening Programme, CervicalCheck, had committed to making this switch. In preparation for HPV primary screening, Coombe Women and Infants University Hospital, which houses the only remaining accredited Public Hospital Cervical Cytology Screening Laboratory in the country, had begun a programme of readiness for HPV testing and recently received ISO 15189 accreditation for HPV DNA testing on the Roche Cobas 4800 platform.
The core concept of HPV primary screening is to detect all women with high-risk HPV and thus those women at risk of developing cervical pre-cancer or cancer. Essentially, HPV primary screening is a test of risk for cervical malignancy, rather than of disease. But what about the high prevalence of HPV in our cervical screening population and are all HPV positive women at equal risk? The HPV primary screening approach will require that a positive HPV result is further triaged to take that test of risk into a test of disease. While many triage options exist e.g. p16/Ki67 staining of cytology smears and host gene methylation markers, with some of them being more informative than others, it has been recommended that the Pap test which has served us well so far is used to further stratify HPV positive women. There is no doubt that the addition of further risk stratification tests or the expansion of cytology as a “test of disease” will present opportunities to enhance the specificity of HPV primary screening and further refine the definition of risk.
In the future, we may see a more tailored approach, where the triage test for a HPV positive woman at the beginning of her cervical screening journey is different to a woman near exiting the programme, with HPV vaccination status also a factor. After nearly 80 years since the introduction of the Pap test cervical screening is set to dramatically change for the better with innovation and good science leading the way forward to a better cervical screening programme.
Dr Stephen Reynolds, Dr Helen Keegan, Dr Christine White, Roisin O’Brien,
Stephen Dempsey, Dr Cara Martin, Martina Ring, Prof. John O’Leary.
– on Behalf of the Cytopathology Dept. Coombe Women and Infants University Hospital, Dublin