Recently, the International Papillomavirus Society (IPVS) issued a ‘call to action’ to health authorities to achieve elimination of cervical cancer as a public health problem. ¹ In principle, cervical cancer rates can eventually be reduced to near-zero given the highly effective primary prevention (HPV vaccination) and secondary prevention (cervical screening) interventions now available. ^2,3 But even if these interventions can be deployed very rapidly at a global level, the timeline to elimination is uncertain.

The issue of timing is complex, because HPV vaccination is most effective in younger cohorts prior to HPV exposure. But cervical cancer occurs in mid-adult and older women, and it will thus take several decades for the full impact of vaccination to be realised. Cervical screening has a much nearer-term impact on cervical cancer, but the extent of coverage and level of organisation for screening varies widely between countries. Furthermore, a large body of evidence now demonstrates that primary HPV screening is more effective than cytology in protecting against invasive cervical cancer; so countries introducing primary HPV should be able to accelerate the reductions. ^3,4 So how will all these factors combine to influence the timing of cervical cancer elimination?

It is useful to look at a specific example. Australia is poised to be the first country to approach cervical cancer elimination, since it has now fully implemented all these major prevention interventions. Australia was the first country to introduce a national publicly-funded HPV vaccination program in 2007, with a wide catch-up age range from 12 to 26 years. In 2013, Australia introduced vaccination for adolescent males, and in 2018 the next generation nonavalent vaccine was introduced, which protects against seven carcinogenic types which are associated with ~90% of cervical cancers. Multiple studies have documented the impact on health outcomes: the prevalence of vaccine-included type-specific infections in young women aged 25-35 years has now drop-ped by a factor of 10 (even in unvaccinated females, due to herd immunity), ⁵ the prevalence of anogenital warts has dropped substantially in both females and heterosexual males, ⁶ cervical precancerous abnormalities (CIN2/3) have now dropped by 41% nationally in women aged 2024 years, ⁷ and the rate of excisional treatment has now also fallen in young women. ⁸

Australia has also had a comprehensive organised screening program since 1991, which by 2010 had already halved cervical cancer incidence rates in women aged 25+ years. ⁹ Prompted by the impact of vaccination and established evidence on primary HPV-based screening, on December 1st, 2017, Australia transitioned to 5-yearly screening with validated HPV assays, which is expected to reduce cervical cancer incidence and mortality rates by at least a further 20% (Table 1). ¹⁰ First out comes from a major trial of screening in unvaccinated populations, Compass, have demonstrated that the increased detection of CIN2+ with HPV compared to cytology screening (well docu- mented in unvaccinated populations) is seen even in Australia’s population, with its high vaccine uptake. ¹¹

Recently, we modelled the impact of these multiple interventions on cervical precancerous abnormalities, invasive cervical cancer and mortality, out to 2035 (Figure 1). ¹² Because of the increased sensitivity of HPV testing, it is initially expected to result in an apparent transitional increase in cancer rates due to earlier detection. In the intermediate term, cervical cancer rates are expected to halve (again) by 2035, and mortality rates should remain stable until about 2020, but then decline by 45% by 2035. These findings indicated that both HPV vaccination and primary HPV screening represent significant and timely steps in Australia’s journey towards elimination of cervical cancer.

Thus, the experience in Australia demonstrates that there is potential to drastically reduce the incidence of one of the world’s major cancers in women. However, the large majority of the global cervical cancer burden is in low and middle income countries where access to screening is very limited or non-existent. ¹³ The key will be effective action to fund, implement and monitor widespread HPV vaccination and cervical screening initiatives in these countries, which have the greatest need.

Acknowledgement: This work was funded via a number of National Medical Research Council (NHMRC) Australia grants and the authors are part of C4, The NHMRC Centre of Research Excellence in Cervical Cancer Control.

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