Thanks to human papillomavirus (HPV) vaccination and screening, cervical cancer elimination is on the global agenda and Australia is on track to meet the elimination goal of fewer than four new cases per 100,000 women.
Following the introduction of HPV vaccination in 2007 (including a catch-up program for people up to the age of 26), Australia took its next major step towards elimination by moving from 2-yearly cytology to 5-yearly in December 2017 switched to HPV screening. This change also included the option for underscreened individuals to be screened using a self-collected sample.
Beginning July 1, 2022, self-collection of HPV test samples will be available as a universal option. Being able to offer pickup for everyone will make it easier to encourage screening for under-screened individuals who are are often unaware that self-collection is an option, and removing some previous obstacles related to the restricted eligibility criteria.
In a recent study, we reviewed the first 2 years of the HPV screening program in Australia, including how the referral pathways worked and the use of self-collection.
One thing Australia does differently than most other facilities that have switched to HPV screening is to look for the HPV type detected rather than treating all HPV types in the same way. HPV16 and HPV18 are known to cause more cervical cancer than other types. HPV16 is particularly aggressive, and HPV18 is strongly associated with adenocarcinomas, which are difficult to detect with cytology – over 25 years of cytological screening do not appear to have reduced these cancers. It makes sense to treat these two HPV types more aggressively, and treating HPV16 and HPV18 differently from other types is one of the options recommended in the World Health Organization’s new screening guidelines.
Our analysis of Australia’s experience supports this initial decision to treat the two HPV types differently – among women who were found to have HPV16 or HPV18 on their first HPV screening test, 0.98% were found to have cervical cancer, compared to 0.76%, for example. of those with non-16/18 types and possible high-grade squamous intraepithelial lesion (HSIL) or poorer cytology. Among people with detected HPV16 or HPV18, the risk of detecting cancer was highest in those with high-grade or glandular abnormalities on their liquid-based cytology (LBC) test (which is automatically performed on the same sample if HPV is detected), but even in women with normal cytology, the cancer risk was still 0.32%.
Ninety cervical cancers were detected in women with HPV16 or HPV18 and normal cytology – 61 of which were adenocarcinomas or other non-squamous cell carcinomas. Being able to identify (and eventually prevent) such cancers is one of the advantages of HPV-based screening compared to cytology. Overall, more than 80% of cervical cancers identified by HPV screening were in those with proven HPV16/18 and 20% of these cancers in women with normal cytology.
Women in Australia up to about 39 years of age at the time of this analysis were age-appropriately eligible for free HPV vaccination, so many of them are protected against HPV16/18. As a result, HPV16/18 infections in younger women have become much less common than before the vaccination program.
As expected, we found that detection of HPV16/18 was relatively uncommon (2.2%) in women aged 25-39 years – but when it was detected in women of this age, their risk was CIN3 or worse or specifically harboring cancer, is at least as high and generally higher than the risk in older unvaccinated women. These HPV16/18 infections may have been acquired prior to vaccination (because women in their 30s were vaccinated as older adolescents or young women during the catch-up program and may have already been exposed to HPV) or this individual was not vaccinated – both of which are common in individuals who were vaccinated at the target age of 12-13 years, less frequently. Information on HPV vaccination status, including number of doses and age at which vaccination was received, is not readily available at the time of clinical treatment. But managing people based on the type of HPV detected simplifies management and eliminates this problem—there’s no need to know if someone was vaccinated and when. Detection of HPV16/18 is a good predictor of risk of serious disease, especially cancer.
The remaining non-16/18 oncogenic HPV types are much less likely to cause cervical cancer than HPV16 or HPPV18, but they are relatively common infections – non-16/18 types were detected in about 6.6% of routine screening Testing proven, and up to 17% of testing among 25-29 year olds. The vaccine used in Australia’s National Immunization Program prior to 2018 did not protect against non-16/18 HPV types, so infections with these types remain high even in younger vaccinated cohorts.
As a result of this combination of relatively high prevalence and relatively low risk, women with non-16/18 types on a routine screening test are not referred for colposcopy unless they have high-grade or glandular abnormalities on their triage cytology test; They were initially advised to return for HPV retesting in 12 months and were referred if HPV was still detected at that time. The recommendation to defer referral for colposcopy was supported by evidence review and detailed modelling.
We found that approximately 61% of the women who returned for this retest at 12 months still had non-16/18 HPV types detected, but the majority (90%) still had a negative or low grade showed cytology.
Ultimately, more than 60% of all colposcopy referrals were women who had HPV types other than 16/18 and who had negative or low-grade cytology, but their risk of serious disease was low and extremely low for cancer (3.4 % CIN3 or worse; 0.02% cancer). Cancer risk was higher in patients with non-16/18 HPV types and high-grade or glandular cytological abnormalities, so cytology appears to be a good method of risk stratification in patients with non-16/18 HPV types, at least initially his round of HPV screening.
Based on this finding of a high rate of referrals for colposcopy and a very low risk of disease, the clinical treatment guidelines for women participating in a 12-month follow-up test who have been diagnosed with HPV types other than 16/18 have been amended – most women without high-grade or glandular abnormalities are referred for another HPV follow-up test in 12 months instead of a colposcopy. As a precaution, there are some exceptions, including those who were overdue at the time of their first screening, Aboriginal and Torres Strait Islander women, and those aged 50 or older.
HPV testing is very effective in identifying not only current risk of the disease but also future risk. Based on our results, in the first round of HPV screening, approximately 1.4% of those screened will find a disease for which treatment would be recommended, but more than 90% will be HPV negative, at very low risk, and can be screened again in 5 years .
This leaves a group of possibly around 8% who do not need immediate treatment but have a higher risk of disease in the future and should therefore be followed up sooner than 5 years (currently this is 12 months). So HPV screening means that a relatively small group of women need to be seen more frequently, but the majority can be seen much less frequently than the 2-year interval recommended in the old cytology program. In most cases, people under surveillance have a result within 3 years and could leave surveillance – either their infection is cleared (in most cases) or the disease is identified and can be treated.
Our results reflect the results of the first round of HPV screening in a woman. The risk of detecting serious illness is likely lower in women who return for their next HPV test after 5 years. Infections found in a woman’s second round of screening are more likely to be recent infections, and cervical cancer takes many years to develop.
One of the troubling findings from our review of program data was that at the end of 2019, 45% of eligible participants were overdue for their first HPV test. Although things have improved since then, at the end of 2020 it was still over 30% overdue.
One of the new features of the HPV screening program, aimed at increasing participation, was the option for never and underscreened individuals to use self-collection. We found that in the first 2 years that this was available for never and underscreened participants, there were only 4522 tests on self-collected samples – this equates to a very small proportion (Check eligibilitylimited laboratories that can process samples, confusion about eligibility or policies, or concerns about testing accuracy.
With clear evidence that HPV polymerase chain reaction (PCR) testing works equally well on clinically collected and self-collected specimens, self-collection will become a labeling application for some HPV tests and self-collection a universal option by July 1st In 2022, many of these barriers will be broken down.
Updated self-collection screening guidelines allow for flexibility and innovation while maintaining the important connection between healthcare professionals and their patients. Providing this flexibility and choice to screening participants is the next major step for the National Cervical Screening Program and toward cervical cancer elimination.
Associate Professor Megan Smith is co-director of the Cervical Cancer and HPV Stream at the Daffodil Center and has served on several state cervical cancer screening advisory groups.
Professor Marion Saville directs the Australian Center for the Prevention of Cervical Cancer, a non-profit organization focused on fighting cervical cancer through the provision of laboratory and registry services.
Professor Karen Canfell is the Founding Director of the Daffodil Centre, Professor and Leadership Fellow of the National Health and Medical Research Council, leading key aspects of WHO’s impact and investment in cervical cancer elimination.
The statements or opinions expressed in this article reflect the views of the authors and do not necessarily represent the official policies of the AMA, the MJA or InSight+ unless otherwise stated.
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