The Asia-Oceania Research Organisation in Genital Infection and Neoplasia (AOGIN) recently held its bi-annual conference in Seoul, South Korea, with the theme “Empowering Women, Together against Cervical Cancer”. Despite having many tools that can prevent, screen for and treat cervical cancer, the conference opened with a powerful statement: “Every two minutes, a woman dies of cervical cancer,” announced sitting AOGIN president, Professor Young Tak Kim.

Professor Kim called on every stakeholder in the conference to come together and approach cervical cancer elimination using a multi-pronged approach. From the scientific community to international societies and government bodies, “Together, we can beat cervical cancer,” remarked Professor Kim.

To gain firsthand insights into the progress of cervical cancer elimination, the Lab Insights team attended the conference. Here are some key takeaways.

The importance of using clinically validated assays

Since the introduction of commercially available HPV detection assays about 20 years ago, the market has seen an influx of hundreds of different assays. This wide variety of assays, with their diverse performance characteristics, aims to meet the varied needs of the HPV community, according to Professor Mario Poljak from the University of Ljubljana.

The World Health Organization’s goal to screen 70% of women has created an estimated demand for 1.4 to 1.5 billion tests. As a result, the cervical cancer screening market has expanded significantly. However, with so many assays available, Professor Poljak compares the situation to the ‘Wild West,’ highlighting concerns about the lack of quality and regulation of many assays. He emphasises the urgent need for improvement, stating, ‘We need to improve, as soon as possible.”

Speaking on his most recent publication on the 2023 global inventory of commercial molecular tests for human papillomaviruses (HPV), Professor Poljak focussed attention on using assays in the way they were designed [1]. Failure to do so can and will lead to disastrous consequences.

Professor Marc Arbyn echoed this sentiment, saying “Laboratories must only use clinically validated assays,” and shared the work that his team had been doing to validate assays against the industry standard Meijer guidelines. As more innovation comes to HPV assays, mRNA-based tests have also undergone evaluations, in addition to more tests being validated as comparator tests.

The right test, at the right time

There was an ongoing discourse on various screening methods used in the different phases of screening. Starting with primary screening, Australia, a pioneer in cervical cancer elimination, will start a national campaign in September 2024 to promote self-collection [2]. They do this per the WHO’s recommendations for tailored primary HPV screening and alternative service delivery models. Dr Karen Canfell, Director of the Daffodil Centre, presented evidence that this method of screening has seen a high uptake in communities that had previously never been screened or very low rates of screening, typically in rural areas [3].

While the adoption of validated and regulated tests is crucial for ensuring accurate results, choosing the right screening method at the right time is also essential for reaching diverse populations effectively. With this mixed modality of service delivery, the Australian health body is making significant progress towards its goal of being the first country to achieve cervical cancer elimination.

While professionals in this field understand that a positive HPV test does not necessarily mean cancer, this distinction is not always clear to the average patient. Professor Woo Ying Ling of Universiti Malaya, a clinician with firsthand experience, shared that women who receive a positive HPV result often experience anxiety. This is why she emphasises the importance of evaluating whether it is necessary to screen for low-risk HPV types or additional genotypes beyond the 14 high-risk HPV types most strongly linked to cervical cancer. Ordering inappropriate tests could decrease specificity, increase patient anxiety, and lead to unnecessary interventions. She advocates for a risk-based approach in triage, as it would be more clinically effective and better for patient well-being.

One effective option for triaging HPV- positive patients and stratifying their risk is the use of the p16/ki67 dual-stain biomarker. Professor Tay Sun Kuie of Singapore General Hospital (SGH) is an advocate for such a triage method. Sharing results from a 245-sample study conducted at SGH which evaluated the effectiveness of these biomarkers, his team clearly demonstrated the advantages of dual staining in the triage of HPV-positive patients (non-HPV16/18). This triage method could also save SGD$231 per woman screened as it reduces the number of interventions needed for patient management, making it an attractive health intervention tool for public healthcare institutions.

Several speakers also spoke about the ongoing investigations for other detection methods, including methylation of specific onco-related genes such as PAX1 and JAM3, that have shown good specificity in screening and triage. However, alternative triage methods discussed have longer turnaround times, limited availability, and require further research and trials to assess their effectiveness across different populations and clinical settings.

Improvements to cervical cancer communication

Dr Tran Huong, WHO Regional Director for the Western Pacific, elaborated that while diversity – in terms of population size, socioeconomic status, and geographical distribution – in the APAC region is large, stigma, whether faced or perceived, is still a significant barrier to effective cervical cancer screening. Even with the most accurate and timely tests, this stigma continues to obstruct progress.

“Teaching women to take control of their health is essential,” says Tran. Healthcare providers should tailor their communication about the disease to alleviate fears and combat misconceptions. Dr Huong highlights these strategies and more in the Strategic Framework for the Comprehensive Prevention and Control of Cervical Cancer in the Western Pacific Region 2023–2030 [4].

Stigma knows no geographical boundaries. Dr Patti Gravitt of the National Cancer Institute (USA) shared a study conducted by the Proyecto Precancer Study Group, which looked at the pre-existing stigma associated with HPV and cervical cancer [5]. The study revealed 3 main themes of stigma:

• women who are HPV-positive are sexually promiscuous;
• men are to blame for women’s HPV infections;
• and that being infected with HPV is shameful and should be hidden

“We should normalise HPV as a common and inconsequential infection,” says Dr Gravitt, “no one is to blame.” Addressing these stigmas is crucial, and healthcare providers need to be educated to manage their biases and become trusted community partners who effectively communicate scientific evidence.

AOGIN Position paper

With the rich sharing of experiences and best practices, AOGIN developed its position statement on cervical cancer screening, which was released at the end of the conference as follows:

• AOGIN regions should move towards HPV testing alone as the primary screening method
• Only clinically validated HPV tests should be used
• HPV testing should be done at least twice between 30 – 50 years of age. If resources permit, countries can consider starting at 25 years at intervals of 5 years till 65 years of age
• AOGIN regions should consider introducing HPV self-sampling to improve screening rates. Careful consideration needs to be given regarding the follow-up of those who tested positive on self-sampling
• During the transition period to HPV testing, cytology or VIA could be used as a screening method
• AOGIN supports efforts to ensure equitable cervical screening uptakes
• AOGIN countries should refer to WHO clinical algorithms for triaging HPV-positive tests

Additional material:

Wei, F. et al. (2024) ‘Causal attribution of human papillomavirus genotypes to invasive cervical cancer worldwide: A systematic analysis of the global literature’, The Lancet, 404(10451), pp. 435–444. doi:10.1016/s0140-6736(24)01097-3.

References:

[1] Poljak, M. et al. (2024) ‘2023 Global Inventory of Commercial Molecular Tests for human papillomaviruses (HPV)’, Journal of Clinical Virology, 172, p. 105671. doi:10.1016/j.jcv.2024.105671.

[2] Australian Centre for the Prevention of Cervical Cancer, 2023. Self-collection campaign.

[3] National Cervical Screening Program, 2023. Self-collection for cervical screening at an all-time high.

[4] World Health Organization, 2023. Regional Committee for the Western Pacific: seventy-fourth session. Manila, Philippines, 16–20 October 2023: report of the Regional Director.

[5] Morse, R.M. et al. (2023) ‘“Easy women get it”: Pre-existing stigma associated with HPV and cervical cancer in a low-resource setting prior to implementation of an HPV screen-and-treat program’, BMC Public Health, 23(1). doi:10.1186/s12889-023-17324-w.