With face-to-face conferences and scientific symposiums back on, the Lab Insights team recently attended the 14th meeting of the Asia-Oceania Research Organisation in Genital Infection and Neoplasia (AOGIN 2022). Distinguished speakers from around the world gathered to talk about human papillomavirus (HPV) and the several cancers it can cause, the most notable among them being cervical cancer. Here are some highlights from the 3-day conference.

Asia Pacific’s vaccination and screening challenges

To tackle cervical cancer, one of the most dominant cancers in young women worldwide, the World Health Organization (WHO) recommends a ‘90-70-90’ approach that involves three key pillars: vaccination, screening and treatment. Yet coverage of vaccination or screening is lacking in many parts of the world, including much of the Asia Pacific region.

“With a vaccination programme rate that covers only 40%, Asia is lagging badly behind the Americas and Europe,” noted Professor Suresh Kumarasamy, clinician and adjunct clinical professor at the Royal College of Surgeons in Ireland (UCD, Malaysia campus). This is especially severe as low vaccination coverage means approximately 345 million women are at risk. A lagging vaccine rollout and implementation was further hindered by the low supply of vaccines during the COVID-19 pandemic.

To address these challenges, speakers at AOGIN 2022 brought up recommendations that can be summarised into the following categories:

• More funding to improve vaccine and screening access
• Increased public education and trust in health institutions to address vaccine hesitancy
• Gender-neutral vaccination approach and herd immunity
• School-based delivery of vaccines
• Destigmatisation of cervical cancer and HPV infection

AOGIN 2022 speakers also discussed how various countries in the Asia Pacific region have implemented policies in line with these recommendations, from vaccination leadership in Australia to screening policy in Malaysia.

Vaccination leadership in Australia

The first pillar of the WHO’s 90-70-90 target is to ensure that 90% of girls are fully vaccinated against HPV by 15 years old. Vaccination programmes are critical because they help interrupt transmission risk, according to Dr Suzanne Garland, Director of the Women’s Centre for Infectious Diseases in Australia.

Widely regarded as a pioneer in cervical cancer vaccination, Australia has had many successes in its elimination efforts. Since the introduction of a vaccination programme in 2007, very little high-risk HPV strains are circulating in the community, a fact that can be attributed to the very high vaccination coverage in girls.

In 2018, Australia moved to vaccinate all eligible children, with coverage rates reaching about 70% in adolescent males. “There is no one size fits all approach,” said Dr Garland. “In our messaging, we must be sure not to stigmatise those with infection.”

Projection data provides further evidence of vaccine efficacy [1]. Dr Karen Canfell, Director at The Daffodil Centre in Australia, shared data showing that an estimated 4.9 – 6.0 million cases of cervical cancer can be averted with ramped up HPV 16/18 specific vaccination, and an even larger estimate of  6.7 – 7.7 million cases of cervical cancer with broad-spectrum vaccination.

When public trust in the efficacy and safety of vaccines is undermined, however, the impact is far-reaching. In 2013, safety concerns raised by the public and media reporting in Japan resulted in the ministry of health pausing HPV vaccine programmes. Dr Ryo Konno of the Department of Obstetrics and Gynecology at Jichi Medical University said that surveys and research will soon reveal the ramifications of the 9-year suspension. Even if and when vaccination rates recover and escalate, there is a limit to what this can do for women (and men) who are vaccinated in their post-teen years [2].

The critical importance of screening

The second pillar of the WHO’s 90-70-90 target is to ensure 70% of women would be screened with a high performance test by age 35 and again by 45. Screening has the ability to achieve the targeted 4 or less cases per 100,000 women much earlier [2]. Despite the advantages of high-performance approaches like the HPV DNA test, however, most experts would agree that screening with any test is better than none at all. There are a number of clinically validated assays that are approved for primary screening, which you can find here.

“We have a long way to reaching 70% coverage of screening with a high performance test,” noted Dr Neerja Bhatla, Professor of Obstetrics & Gynecology at the All India Institute of Medical Sciences in India. “Eventually, [implementing] screening programmes will be even more important than the test itself.”

Only 4 out of 10 ASEAN countries have launched a population-based screening, with most women screened opportunistically or not at all. This lack of access to screening can be due to many factors, ranging from the lack of financial resources to pay for a test to the low quality of testing infrastructure within a country.

Effective cervical cancer screening programmes are worth the investment as they can improve outcomes and reduce costs to health systems and women. The benefits can also extend to the broader economy, with an estimated USD $3.20 return for every dollar spent on intervention measures, and up to USD $26 when this support is extended to broader aspects of a woman’s life [3].

To reap all the benefits from screening programmes, having good follow-up services is important. For Professor Jautpol Srisomboon of Chiang Mai University, the practice in his region for follow-up is predominantly colposcopy due to the low cost. Yet this practice comes with its own set of challenges, such as  20-40% loss to follow-up, the emotional stress of waiting, and women incurring more expenses due to these multiple visits. Srisomboon said that introducing HPV DNA testing for primary screening in Thailand across all 77 provinces in 2023 would reduce the expected workload from colposcopies to an estimated 2% of all screened women.

Screening is especially important in some minority populations, such as those living with HIV. In APAC, there are about 6 million adults and children living with HIV, second only to the highly burdened regions of East and Southern Africa.  With a compromised immune system, HIV-infected women are 6 times more likely to develop cervical cancer due to their inability to clear what should be a transient HPV infection [4].

Dr Annette H Sohn, paediatrician and Vice President and Director of TREAT Asia at amFAR, argued that women living with HIV should be screened earlier, and screened with HPV DNA tests more frequently. She highlighted that there is no one set of guidelines for the management of HPV in this population, and called for efforts to close the research gap.

The power of self-sampling

Many countries are also exploring self-sampling approaches to make it easier for more women to get tested. These approaches are beneficial in places where women’s health issues are culturally sensitive and for women who may hesitate before visiting a doctor for sample collection. Being easily transportable, they are also beneficial for remote and low-resource settings where access to testing services is limited.

Professor Woo Yin Ling, Consultant Gynaecological Oncologist at the University of Malaya Medical Centre and Founder of Program ROSE (a community-based screening programme in Malaysia) spoke about the use of self-sampling as a possible replacement for conventional methods. Allaying concerns regarding the validity of the tests, she shared a list of papers (see below under additional resources) that show good concordance of results between self-sampled and healthcare worker collected ones.

While not yet part of any national guidelines, urine-based HPV tests are another approach to self-sampling that may have advantages in settings where vaginal swabs are not as readily accepted. Studies run in the past few years have shown good concordance between first void urine samples and vaginal swab samples, but current research is limited to small subject groups and most experts agree that more evidence is needed to evaluate this method [5].

Additional Resources:

Arbyn, M. et al. (2018) “Detecting cervical precancer and reaching underscreened women by using HPV testing on self samples: Updated meta-analyses,” BMJ [Preprint]. Available at: https://doi.org/10.1136/bmj.k4823.

Polman, N.J. et al. (2019) “Performance of human papillomavirus testing on self-collected versus clinician-collected samples for the detection of cervical intraepithelial neoplasia of grade 2 or worse: A randomised, paired screen-positive, non-inferiority trial,” The Lancet Oncology, 20(2), pp. 229–238. Available at: https://doi.org/10.1016/s1470-2045(18)30763-0.

Saville, M. et al. (2020) “Analytical performance of HPV assays on vaginal self-collected vs practitioner-collected cervical samples: The scope study,” Journal of Clinical Virology, 127, p. 104375. Available at: https://doi.org/10.1016/j.jcv.2020.104375.

References:

[1] Simms, K.T. et al. (2019) “Impact of scaled up human papillomavirus vaccination and cervical screening and the potential for global elimination of cervical cancer in 181 countries, 2020–99: A modelling study,” The Lancet Oncology, 20(3), pp. 394–407. Available at: https://doi.org/10.1016/s1470-2045(18)30836-2.

[2] Burger, E.A. et al. (2020) “Projected time to elimination of cervical cancer in the USA: A comparative modelling study,” The Lancet Public Health, 5(4). Available at: https://doi.org/10.1016/s2468-2667(20)30006-2.

[3] A cervical cancer-free future: First-ever global commitment to eliminate a cancer. World Health Organization. World Health Organization. Available at: https://www.who.int/news/item/17-11-2020-a-cervical-cancer-free-future-first-ever-global-commitment-to-eliminate-a-cancer (Accessed: December 8, 2022).

[4] Stelzle, D. et al. (2021) “Estimates of the global burden of cervical cancer associated with HIV,” The Lancet Global Health, 9(2). Available at: https://doi.org/10.1016/s2214-109x(20)30459-9.

[5] Ørnskov, D. et al. (2021) “Clinical performance and acceptability of self-collected vaginal and urine samples compared with clinician-taken cervical samples for HPV testing among women referred for colposcopy. A cross-sectional study,” BMJ Open, 11(3). Available at: https://doi.org/10.1136/bmjopen-2020-041512.