Dra. Conceição Saldanha

Pathology Medical Deputy Director and Cytopathology 

Dra. Mariana Costa

Molecular Pathology Manager 

New strategies for cervical cancer screening

HPA Magazine 23 // 2025

Cervical carcinoma (CC) is still one of the most prevalent neoplasms worldwide, despite being one of the most studied carcinomas and experiencing the greatest decrease in mortality and incidence in recent years.
In Portugal, in 2020, the age-standardised incidence was 10.7/100,000, and mortality was 3.2/100,000.

In November 2020, the WHO launched a global challenge to accelerate the elimination of CC based on three key strategies: vaccination, screening, and treatment. The successful implementation of these three points and the achievement of these targets could reduce the emergence of new cases by more than 40% and prevent 5 million deaths by 2050.
CC screening, using cytology as the detection method, has contributed to a decline in CC incidence and mortality over the last 60 years. However, the emergence of molecular biology techniques has revolutionised the study of CC, confirming that HPV infection is the main culprit in the development of cervical carcinogenesis, which begins with an acute infection by one or more carcinogenic viral subtypes of HPV. Vaccination has been decisive in reducing the incidence of cancer, but it has also brought new challenges due to the replacement of the most frequent viral subtypes, leading to the need for new hr-HPV genotyping tests (high risk).
Scientific evidence has shown in recent years that screening with HPV testing has surpassed cytology in sensitivity, contributing to better prevention of CC. The results of screening tests such as cytology and hr-HPV detect situations of infection whose risk of disease progression is minimal.
Therefore, after screening, additional triage tests are necessary for reliable clarification, such as extended hr-HPV genotyping, CINtec® PLUS, or hypermethylation (epigenetics). Colposcopy, with biopsy, if necessary, is a mandatory procedure for assessing patients with a clinically suspicious cervix.
The primary challenge of CC screening is to identify lesions with the potential to evolve. To avoid discomfort and anxiety for both patient and clinician, and considering potential a conservative approach to potential interference in the patient's obstetric future, a reliable test is needed to provide a clearer and more objective recommendation, ensuring the absence of significant disease and/or delaying the need for follow-up examinations.
A pre-existing HPV infection can lead to genetic instability of the infected cells and consequently to the development of cervical cancer. In the course of carcinogenesis, changes occur, particularly in DNA methylation patterns, which have demonstrated their clinical potential as predictive biomarkers of disease progression. GynTect® is a rapid, non-invasive test for clarifying abnormalities in cervical cancer screening, facilitating clinical follow-up decisions and assessing the need for colposcopy. For this test, cervical-vaginal cytology or cytology from the vaginal vault collected in ThinPrep® is used. The GynTect® assay recognises six areas of the human genome that are only methylated in oncogenesis. A negative GynTect® result excludes a diagnosis of cancer at the time of the test, and if dysplasia is present, its progression is highly unlikely. A positive GynTect® result is predictive of a malignant precursor lesion or cancer, and immediate clinical counselling is recommended.
The GynTect® test shows high sensitivity and specificity in detecting CIN3+ lesions. GynTect® is less sensitive for detecting CIN1 and CIN2 lesions, so these results should be evaluated considering that many of these lesions regress spontaneously, especially in younger women.
Studies indicate that GynTect® reliably detects all cervical cancers, and lesions with a negative GynTect® result do not progress to carcinomas. This approach not only reduces costs but also has the ability to mitigate anxiety, overdiagnosis and overtreatment.
At Eurogin 2024, a study was also presented by LAP's Molecular Biology department, the conclusions of which emphasise the potential of methylation testing to improve the efficiency and accuracy of cervical cancer screening tests.

Of all the screening strategies mentioned, methylation is the one with the best correlation with the oncogenesis process, providing greater prognostic value.
The LAP has a large team of differentiated pathologists dedicated to the different areas of the speciality. The gynaecological pathology service offers high-quality diagnostic cytology and histopathology in cytologies, biopsies and resections of the urogenital tract. Unilabs also has a multidisciplinary team that is highly specialised in conducting molecular biology studies, comprising doctors, biologists and qualified technicians. With this expertise, it is possible to offer more precise guidance in the follow-up of patients.

Referências Bibliográficas // References
Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests by the SPCPTGI. Pedro A, Pacheco A, et al.  Acta Med Port [Internet]. 2023 Jan. 23 [cited 2024 Dec. 12]; 36(4):285-9.
Evaluation of host gene methylation as a triage test for HPV positive women - a cohort study: P. Baptista, M. Costa, J. Hippe, C. Sousa, M. Schmitz, A. Silva, A. Hansel, M. Preti JLGTD (2024).
Evaluation of a host DNA methylation panel in a high HPV prevalence cohort. C. Sousa; C. Saldanha; M. Costa; S. Esteves Eurogin Poster (2017).
Triage of hrHPV-positive women: comparison of two commercial methylation-specific PCR assays: Dippmann et al, BMC (2020).
Performance of a six-methylation-marker assay on self-collected cervical samples – A feasibility study: Klischke et al, Journal of Virological Methods (2021).
Psychological distress in cervical cancer screening: results from a German online survey: M. Jentschke et al, Archives of Gynecology and Obstetrics (2020).
Studie zu CINtec Plus und cobas HPV im Vergleich zu GynTect: Schmitz et al, BMC Cancer (2018).
A Promising DNA Methylation Signature for the Triage of High-Risk Human Papillomavirus DNA-Positive Women: Hansel et al., PLOS ONE (2014).