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Faculty and Disclosures

Associate Professor Marion Saville

MBChB, Am Bd (Anat Path & Cytopath), FIAC, Grad Dip Med (Clin Epi), GAICD
Executive Director and Public Officer,
Victorian Cytology Services, Australia

 

Associate Professor Saville has served on numerous cervical screening advisory committees in Australia and New Zealand. Most recently she was a member of the Renewal Steering Committee, a group established by Australian governments to provide oversight to “Renewal” of the National Cervical Screening Programme and is currently a member (Deputy Chair) on the Working Party to draft “Clinical Management Guidelines for the Prevention of Cervical Cancer”.

 

Our Moderator

Dr Wichai Termrungruanglert

Chairman, Department of Obstetrics and Gynecology
Associate Professor in Gynecologic Oncology
Faculty of Medicine
Chulalongkorn University, Bangkok, Thailand

Secretory General, Thai Gynecologic Cancer Society (TGCS)

 

Dr Wichai has been very active in the prevention of cervical cancer and development of screening guidelines with primary HPV testing in Thailand. He obtained obstetrics and gynaecology specialty with gynae-oncology subspecialty from Chulalongkorn University Thailand and fellowship from The University of Texas MD Anderson Cancer Center, USA. He is a clinical consultant and lecturer with several published clinical papers including a recent cost-effectiveness analysis study of HPV testing as a primary cervical cancer screening tool in Thailand.

 

Invited speakers did not receive any honorarium from Roche Diagnostics.

Webinar: Why is there a need to change from Pap smear to HPV DNA testing?

What you will learn:

  • The need for an effective screening programme to eradicate cervical cancer
  • Australia's success story on screening programme with Pap smear
  • Introduction of HPV DNA testing versus Pap smear as a primary screening tool
  • The rationale and considerations on implementing HPV DNA testing as primary screening instead of co-testing
  • The relevant aspects to consider when switching from Pap smear to HPV DNA testing
Q & A during the webinar
  • Q. Why do we need to use HPV test?

    A. The HPV test offers better sensitivity for the detection of CIN2+ than cytology or VIA and therefore supports much longer screening intervals.

  • Q. Can low risk HPV type positivity implicate high risk type?

    A. The currently used tests don't test for low risk types. The presence of low risk HPV just indicates potential exposure to other types.

  • Q. Can you share some information on the health economics analysis to implement screening with HPV testing?

    A. Health economic assessment needs to be done within specific country context. The Australian evaluation was recently published. https://www.thelancet.com/pdfs/journals/lanpub/PIIS2468-2667(17)30007-5.pdf

  • Q. How does Cobas Platform compare with the GeneXpert platform in a "screen and treat" option in a screening program?
    Is there a health economics model based on cobas platform based testing in cervical cancer screening globally?

    A. The platforms have similar performance from a sensitivity and specificity point of view. The GeneXpert platform enables point of care testing that isn't possible in the same way with the cobas platform. However, the GeneXpert tests are considerably more expensive in most markets.

  • Q. What is the recommended screening protocol for young women under 30 years?

    A. Screening women younger than 30 with HPV tests is likely to be problematic in countries that have not yet had HPV vaccination programs with high coverage and probably isn't recommended.

  • Q. What will be the role of cytoscreener & cytopathologist given that the workload will be remarkably reduced?

    A. The role of the cytopathologist has not changed much in Australia since the same abnormalities are still there but a lot of cytoscreeners have moved out of the industry in Australia since we mostly don't do cytology now if women are HPV negative.

  • Q. What are the management of HPV positive other genotypes, can we use biomarkers (Dual-stain technology)?

    A. At present, the Australian program uses LBC to triage women with HPV (not 16/18). The Compass trial is comparing LBC with Dual-stain in this setting. https://bmjopen.bmj.com/content/8/3/e016700corr1

  • Q. To my mind, question is not about need to changing from Pap. It’s about how do we justify cost effectiveness for HPV in the insufficiently resourced countries where screening is non-existent and HPV is seen as the most expensive arm of screening. The other question may be, how do we handle the proliferation of clinically non-validated tests (mostly on PCR platforms) in the largely unregulated markets like India.

    A. Agree with the challenges. Would just point out that the cost of an HPV test should not be compared with the cost of a single cytology or VIA examination. The protection from one negative HPV result would probably need around 3 cytology tests for equivalence. Note comment on difficult regulatory environment

  • Q. How many developing countries have shifted from Pap smear screening to HPV testing??
    What is the main mode of cervical cancer screening in the United States?

    A. Pilot studies are underway in a number of developing countries and I would hope that these studies lead to rapid scale up to national programs. In the US co-testing (HPV and cytology on all women) is most common but countries with organised screening (Australia, NZ, Canada and Europe) are all working towards HPV only screening programs. The Netherlands went live first and Australia second, late last year(2017).

  • Q. Is there a role for HPV testing in adolescents with early sexual exposures?

    A. There is no evidence that earlier testing is needed or even works in young women with early exposure. However, as you may know the Australian program allows (but does not recommend) a single test between the age of 20 and 24 in some settings. Please check the Guidelines very carefully. https://wiki.cancer.org.au/australia/Clinical_question:Women_experienced_early_sexual_activity_or_victims_of_abuse

  • Q. What is your experience on establishing Cervical Cancer Screening using cobas HPV testing in Australia?

    A. Our lab has both the cobas 6800 and cobas 4800 technology, as well as other HPV platforms. The cobas 6800 has been necessary to support the volumes of tests required, over 1,000 test per day.

  • Q. Is testing of cervical Pap smear together with HPV testing more reliable than only Pap smear?

    A. Co-testing is more sensitive than Pap smear alone, but not much more sensitive than HPV alone therefore we don't recommend co-testing. The HPV test is more sensitive than the Pap.

  • Q. Do you need to perform HPV screening in early HPV vaccinated girl?

    A. If resources allow, women that have been vaccinated with the 4-valent HPV vaccine should still be screened since the 4-valent vaccine is only expected to prevent around 70% of cervical cancers. This will be very different once girls vaccinated with the 9-valent vaccine reach screening age since the 9-valent vaccine is expected to prevent 90% of cervical cancers.

  • Q. Do we need to screen males with HPV testing?

    A. No, but high income countries do commonly vaccinate males.

  • Q. What are the chances of HPV infection or cervical cancer in women who are not sexually exposed?

    A. Virtually zero, our Australian program does not recommend screening for women with absolutely no sexual exposure but all other women are recommended t be screened.

  • Q. What is the significance of biopsy positive CIN 1 with HPV negative test 2 per 50 cases?

    A. Probably not unexpected. Remember that tests currently in use only test of "high risk" HPV the types associated with cancer. They don't test for HPV 6, 11 or other low risk types not associated with cancer. However, these types can produce LSIL (including CIN1) appearances on biopsy.

  • Q. How do you convinced the administrator to fund the service and overcome the financial burden?

    A. In high income countries it is about showing cost effectiveness. The Australia cost-effectiveness evaluation was published. https://www.thelancet.com/pdfs/journals/lanpub/PIIS2468-2667(17)30007-5.p

  • Q. Australia is such a big country. How do you ensure every woman comes for the screening and how do you keep up with the follow-up (keep tract of the women, to come for follow-up)?

    A. In Australia we have had cervical screening registers for several decades, for example see http://www.vccr.org/. At VCS we think this is important for developing countries implementing screening or changing to HPV to support these developments with registers. We are trialling this approach in Malaysia at the moment, see https://www.vcsdigital.com.au/case-studies/project-rose-removing-obstacles-to-cervical-screening-in-malaysia

  • Q. Is there any update on Cervical Cancer vaccination after treatment of Pre invasive/dysplastic cervical lesions (CIN2-3, high grade CIN post excision) and what is the optimal timing to start vaccination in this subgroup of patients?

    A. I couldn't answer this better than to refer you to this article by my colleagues. https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/ajo.12227

  • Q. For young women less than 25 years of age, with high risk behaviour (ie. escorts) with a normal LQBC smear but detected other high risk subtypes HPV not covered in G9 vaccine: is it advisable to vaccinate these patients and repeat HPV DNA test later? if yes, what is the recommended interval after completion of vaccination to re-test the HPV DNA and what is the optimal follow up or treatment strategy for this high risk group of patients?

    It is well known that Vaccine is not intended for treatment, but the diverse patient profile that we face in clinical practice poses a lot of challenges and questions as to how best manage the above patients that I have mentioned.

    A. Women under 25 years probably don't need to be screened regardless of sexual behaviour but they should definitely be screened at 25 and beyond. If the woman can afford vaccination at this age and hasn't already been vaccinated, then there may be considerable benefit and the vaccines are very safe. If the woman has had 4-valent vaccine (2 doses) then 9-valent vaccination isn't recommended, see more here http://www.hpvregister.org.au/site/DefaultSite/filesystem/documents/Health-Professionals/18006_NHPVR.VAC.PROVIDER.ART.2.web.pdf

  • Q. What should developing countries do considering 80% of CxCa detection rate and currently reliability for VIA/VILI tests as we’ve never thought of Pap test regardless of its non-specificity?

    A. Countries with well-established VIA programs may be ready to build on this using HPV tests. If VIA is only needed in women with HPV, then the reach of screening could be increased by around a factor of 10. Women who are HPV positive should be treated at VIA regardless of VIA appearances because unfortunately VIA is insufficiently sensitive to be sure that an HPV positive woman with normal VIA appearances doesn't have a pre-cancerous lesion.

  • Q. What will be the trend of expected cost for an HPV screening in the next 5 years?

    A. I am very hopeful that as demand for these tests increases, we will continue to see cost reductions, particularly for developing countries where these tests are needed most.

  • Q. Do we need to do HPV DNA testing in NILM PAP Smears?

    A. No, not if you are prepared to rescreen at 3 years. If you want to offer the same protection with less frequent screening, suggest consider HPV test instead of Pap.

  • Q. What is the HPV platform used in Australia?

    A. A variety of platforms are in use. All platforms must conform to technical requirements published by the Australian government. This is enforced through the accreditation of laboratories.

  • Q. Is co-infection with 2 or more high risk types known? If yes, what are the implications for cervical cancer?

    A. Yes, HPV prevalence studies show that co-infection is quite common. It is probably the presence of the most oncogenic type (!6/18 vs others) that drives the cancer risk.

  • Q. What are the key factors driving higher coverage rate for CxCa screening in Australia?

    A.Investment by governments (mostly state and territory governments) in promoting screening particularly among under-screened groups. Our cancer screening registers write to women who are overdue for screening to remind them of the importance of attending.

  • Q. The re-testing interval is up to 5 years, can you share how can manage the ratio of women come back for re-testing?

    A. This has been a bit difficult in Australia because we are transitioning from a very well established 2-year interval to a 5- year interval creating fluctuating demand for laboratories over the next several years. In our lab, the early understanding that this was happening enabled us to plan our resources accordingly. See https://bmchealthservres.biomedcentral.com/articles/10.1186/s12913-016-1375-9

  • Q. How do we convince the cytologists to migrate from cytology-based into HPV test-based primary screening?

    A.This has been a very big challenge in Australia where we have a very big workforce, because we had very good coverage and relatively high frequency of screenings, and I guess ultimately, it’s not the cytologists who decide, it’s the Department of Health and the Australian government decides. I’m not going to downplay that it has been a very painful and difficult transition in Australia, where I lead an organization that used to employ 50 scientists and now we’re about 12, I think. That was a difficult process, but in the end. our organization took the view that we had to recommend what was best for women, that we can’t keep doing something when we know something else is better because it requires that sort of change, and it’s like all the technology change affecting society, it’s disruptive and it’s difficult, and you manage it as best you can. I guess that’s really all I can say there. I think it is different in countries that don’t already have established Pap programs. You probably don’t even have enough scientists now to read Pap if you were to screen every woman every three years, which is what you would need to do. So I think it’s a more difficult problem for countries with established programs.

  • Q. What is the optimal interval of the cervical cancer screening with the HPV test?

    A. I would say absolutely optimally, you wouldn’t do any more than every five years in a high-income setting, but what we are starting to see is that even within countries, this idea of resource stratified guidelines for screening, you can do an awful lot with one test in a woman’s life between 30 and 49. Somewhat more, If you do it twice in a lifetime, you can do 10 yearly or five yearly is the absolute maximum screen that you would do when you have a good amount of resource to put into this. So, I guess the answer depends on how much resource you’ve got available to put into cervix cancer prevention in your country and it’s not just the primary screening test you have to account for, it’s the downstream management of HPV positive women, you have to cross that out too.

  • Q. Are there any guidelines for the cellularity control for HPV PCR?

    A. Some of the tests have a cellularity control and some of the tests don’t, and that’s without becoming very commercial about this, because we prize our independence at VC is that something you have to ask the test manufacturer, is there a cellularity control in this test? I think I’m not talking out of school to say that the Roche tests do have a beta-globin control which qualifies as a cellularity control. Each test, it’s a question, some do, some don’t, and it needs to be answered.

  • Q. Is there any treatment method or drug in the treating of 16 and 18 positive patients?

    A. As far as I’m aware, there is no treatment for HPV infection. We treat precancerous lesions is the bottom line. That’s what we do. In the low-income countries, what we’re saying is cryotherapy to the cervix will treat any lesion that is present and there will be a number of women who have lesions present, and will also set up a wound healing and repair process that exposes the virus into the immune system, and therefore will treat the HPV, but the primary goal is to treat any lesion that’s present.

Please contact your local Roche representative should you have any questions on the above Q&A