Expert Review by Jessica Darlington-Brown, UNSW Australia.
Jessica Darlington Brown provides Oncology News Australia with in-depth coverage of studies presented at the UICC World Cancer Congress on cervical cancer screening, HPV vaccination and the ipap trial.
Australia was the first country to implement a national publically funded HPV vaccination program. In 2007 a school-based program for females aged 12-13 was introduced, this included a school-based catch up program for girls aged 13-17 and a GP based catch up program for women 18-26 until 2009. This was extended to include routine school based vaccination of boys aged 12-13 in 2013, with a 2-year catch up for boys aged 14-15. Reported coverage of the 3-dose vaccine in the school program ranged from 62% to 74% in females aged 12-17 and slightly lower (17%-42%) in women aged 18-26 years (Smith et al 2014). National coverage data for males has not yet been released. Early data suggests that the impact of the program has been considerable with a decrease in disease rates already observed in younger women.
There has been a reported drop in high grade (HG) abnormalities observed in women offered the HPV vaccine. A recent population based study reported a significantly lower rate of histologically confirmed high-grade cervical in women who were vaccinated (any dose) HG 4.8/ 1,000 compared with unvaccinated women HG 6.4/1,000. (Gertig et al 2013).
Furthermore, following the implementation of the HPV vaccination program there has been a reported reduction of genital warts diagnosed in the general and indigenous populations of Australia. An analysis of national population based hospital data reported a decrease in admission rates for genital warts, from mid- 2007 in females aged 12-17 years old. Similar reductions were observed in female Indigenous population aged 15-24 years old. Since the implementation of the HPV vaccination program there has been 1000 fewer hospital admissions involving warts diagnoses during 2010-2011 (Smith et al 2014).
Renewal of the National Cervical Screening Program in Australia
The National Cervical Screening Program (NCSP) has been incredibly effective at reducing the burden of cervical cancer in Australia since its introduction in 1991. Current recommendations involve 2 yearly screening in women aged 18-64 with the Pap test. There has been a significant decrease in the mortality and incidence from cervical cancer. However following the success of the NSCP and the introduction of the HPV vaccination program there has been emerging evidence that led to the Australian government initiating a review of the NCSP in Australia.
The review (‘Renewal’) of the NCSP aimed to ensure that the screening program continues to be effective in light of the recent introduction of the HPV vaccination program and advances in cervical screening technology. The Australian government initiated the renewal process in November 2011 and in April 2014 the results of phase one of the Renewal were reported. The Medical Services Advisory Committee (MSAC) recommended that Australia move towards a five yearly screening program, using HPV DNA testing as the primary test. The age of commencement was recommended to increase to 25 with an exit test at age 70. It is anticipated that these changes to the program will begin to be implemented in late 2016 early 2017. More information can be found here http://www.cancerscreening.gov.au/internet/screening/publishing.nsf/Content/ncsp-renewal
Almost half of all women who present with an invasive or micro-invasive cancer in Victoria have either never participated in cervical screening or were last screened more than 2.5 years prior to diagnosis. There have been numerous strategies to improve cervical screening in these high risk, ‘hard to reach’ groups, however most have had minimal success. The ipap trial is a randomised controlled trial aiming to evaluate whether mailing HPV self-sampling kits to women who are either under screened or never screened will increase participation in the screening program. Participants are aged 30-69 who either have no record on the Victorian Cervical Cytology Registry (VCCR) or their last Pap test was 5 to 15 years ago. Women are sent either a self-sampling kit which is returned to the Victorian Cytology Service (VCS) for testing, or a reminder to attend for a Pap test. Preliminary results reported at the conference suggest an increase in screening in ‘never’ and ‘under-screened’ women who were sent a self-sampling kit. Formal results from the ipap trial are expected to be published in 2015.
New directions for Cervical Cancer Screening in Australia
Compass is a randomised controlled trial of Primary HPV DNA testing for cervical cancer screening in Australia. Compass will act as a sentinel experience for Renewal. The trial will compare 2.5 yearly liquid based cytology with 5 yearly HPV DNA testing in women offered vaccination (vaccinated), and women not offered vaccination (unvaccinated). Recruitment of 120,000 women will occur in general practice and sexual health clinics, initially in the state of Victoria, with the possibility of extending to other states in the future. Eligible women aged 25-69 will have a liquid based cytology LBC sample collected as part of their routine cervical screening examination and this will be sent to a centralised laboratory where it will be randomised into one of two study arms. Study arm A (control arm) will involve 2.5 yearly image read cytology screening with reflex HPV triage testing for low grade cytology. The Intervention (HPV) Arm study arm B will involve 5 yearly HPV screening with partial genotyping enabling detection of 14 potentially oncogenic types with separate identification of HPV16 and HPV18 and secondary randomisation of “Intermediate risk” women testing positive for oncogenic HPV (but not HPV 16 or 18) to either image read LBC screening or dual-stained (DS) cytology testing (with p16/Ki67). A routine laboratory report issued to practitioners will specify the recommended management according to study arms and the test results. Women will be flagged in the Victorian Cervical Cytology Registry as participating in the Compass Trial and will have invitation letters issued at 3 months prior to the specified time for follow-up or re-screening. Data linkage between the VCCR and the National HPV Vaccination Program Register will be performed and women will be followed for 5.5 years from the time of recruitment.
Ethics approval is expected to be received in mid-December and recruitment for Compass will begin in late December 2014. Recruitment is expected to occur over 2 years with baseline results expected mid to late 2015. Further information can be found at www.compasstrial.org.au
Jessica Darlington-Brown is a Project Co-ordinator at the Lowy Cancer Research Centre, UNSW Australia .
Gertig. D., Brotherton. J., Budd. A., Drennan. K., Chappell. G., Saville. M., 2013 Impact of a population-based HPV vaccination program on cervical abnormalities: a data linkage study BMC Medicine, 11:227 doi:10.1186/1741-7015-11-227.
Smith. M., Liu. B., McIntyre. P., Menzies. R., Dey. A., Canfell. K., 2014 Fall in genital wart diagnosis in the general and indigenous Australian population following implementation of a national human papillomavirus vaccination program: analysis of routinely collected national hospital data, Journal of Infectious Diseases, DOI: 10.1093/infdis/jiu370.