Transforming cervical cancer screening: Dr Mariana Costa's insights from EUROGIN 2024

Last March, our colleague Dr Mariana Costa was invited to participate in EUROGIN, the world's premier international congress on HPV infections and associated cancers, with a focus on prevention and diagnostics, held in Stockholm. During her presentation, Dr Costa introduced a pioneering project on the latest advancements in HPV testing and the potential of DNA methylation to transform cervical cancer screening, which the Molecular Biology Laboratory team at Unilabs Portugal conducted in collaboration with prestigious medical institutions such as the Lower Genital Tract Unit, Centro Hospitalar de São João, Porto, Portugal; Department of Gynecology-Obstetrics and Pediatrics, Faculty of Medicine – University of Porto, Porto, Portugal; Oncgnostics GmbH, Jena, Germany; and the Department of Surgical Sciences University of Torino, Italy.

The primary objective of this study was to evaluate the impact of incorporating a methylation assay into the triage process for high-risk HPV positive cases, compared to the standard of care. The findings revealed that the Gyntect methylation test exhibited high sensitivity and specificity for detecting cervical intraepithelial neoplasia grade 3 or higher (CIN3+), significantly reducing the rate of referrals for colposcopy. Moreover, the level of methylation demonstrated a positive correlation with the severity of the disease, indicating its potential as a prognostic.

The study's conclusions underscore the potential of methylation testing to improve the efficiency and accuracy of cervical cancer screening programmes. By implementing a triage strategy that combines HPV16/18 testing with methylation analysis for other high-risk HPV types, healthcare providers can effectively identify individuals at higher risk of developing cervical cancer while minimising unnecessary referrals for further diagnostic procedures. This approach not only reduces healthcare costs but also mitigates patient anxiety, overdiagnosis, and overtreatment.

In an exclusive interview, Dr Costa shared her perspective on the implications of her research and the future of cervical cancer screening. 

What inspired you to delve into the field of molecular pathology and cervical cancer screening?

I started working on cervical cancer screening in cytology diagnosis around 16 years ago and had a great mentor, Dr Conceição Saldanha. She always aimed to differentiate the lab from other competitors by committing to scientific investigations and experimenting with new technologies based on what she learned from the leading international specialists. Fortunately, this was very much in line with my view. Trying new tests, validating them, and seeing them implemented successfully is very rewarding to me. The study of cervical cancer has undergone major transformations since I started working, from the development of vaccines to the increasingly complex treatment algorithms. It has been fascinating to witness this evolution toward a highly preventable and curable disease in my lifetime. 

How do you envision the implementation of methylation testing alongside HPV16/18 testing in cervical cancer screening programmes, considering its potential to improve efficiency, accuracy, and patient outcomes while reducing healthcare costs?

In the Portuguese context of primary screening with HPV testing, incorporating methylation analysis for HPV-positive cases of other high-risk HPV types could significantly reduce the need for colposcopies. Currently, coloscopies are often delayed due to extensive waiting lists, yet the methylation approach ensures the detection of CIN3+ lesions without compromise. Moreover, there is a prevalent trend of opportunistic screening in private practices in Portugal, where co-testing is used (HPV test and cytology). Methylation analysis offers a more comprehensive assessment, providing a deeper insight into the risk of disease and boasting a notable negative predictive value. This helps manage patient’s anxiety, which is very relevant for the relationship between patient and gynecologist. 

How do you see the future of HPV-related research evolving in the coming years?

The oncogenesis of the cervical cancer has been very well studied in recent years, and the vaccine has significantly reduced mortality rates. However, infection rates remain high, and while there is a decrease in HPV 16/18 cases in countries with the vaccine, the significant migratory flow seen in Portugal and other European countries presents challenges in defining management algorithms for these patients. The management options have remained unchanged for years, so it is really up the laboratory to increase the sensibility and specificity of the tests used. Improved vaccines offering specific protection for other HPV types and possible cross protection to others may help. Studies correlating other morbidities and infections, such as the impact of the microbiome, should be addressed. There is much to be done regarding other tumours related to HPV, such as anal cancer, head and neck cancer, penile cancer, vulvar cancer…

What are some potential next steps for further advancing the effectiveness of cervical cancer screening protocols?

Increasing the reach of the screening is crucial, and self-collected samples offer a good option, particularly when compliance with screening is low. We should also enhance patient education to raise awareness about screening and vaccination. We can emphasise risk-based screening, considering individual risk (screening history) as well as the HPV type. Furthermore, integrating and using AI for image analysis in cytology can improve the classification of abnormal cervical lesions. AI could play a significant role in designing appropriate algorithms, as decision-making regarding follow-up options has become increasingly complex. 

Could you elaborate on any future research projects or collaborations you're excited about?

We are excited about several ongoing projects. In terms of methylation, we are exploring the potential of using different sample types and investigating other types of neoplasms. We are also working on the identification of some cancer inducing microorganisms and antibiotic resistances. I am hopeful that we will soon publish some results and unveil our findings.