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Printable Handouts
Navigable Slide Index
- Introduction
- Talk outline
- HPV16 double stranded circular DNA genome
- Papillomavirus virion
- HPV life cycle in a stratified squamous epithelium
- Incidence of cancers attributable to HPV (World)
- Incidence of cancers attributable to HPV (USA)
- Female reproductive tract (anatomy & histology)
- From cervical HPV infection to cervical cancer
- Rapid acquisition of HPV infection
- Primary and secondary prevention methods
- Prophylactic HPV vaccines
- Three distinct HPV L1 VLP vaccines
- Timeline of HPV and vaccine development
- Progression from HPV infection to cervical cancer
- Efficacy of HPV VLP vaccines
- FDA approval of Gardasil-9
- Vaccine protection against pre-malignant lesions
- HPV vaccines are well established products
- HPV VLP vaccines: an excellent safety record
- Vaccine effectiveness
- Prevalence of HPV before and after vaccination
- Reduction in CIN2+ cervical dysplasia by Gardasil
- Projection of cervical cancer cases prevention
- HPV vaccine uptake in females
- Increasing vaccine uptake
- Surprising one dose efficacy of cervarix
- HPV cases 7 years post vaccination in Costa Rica
- One dose clinical trials
- Why do HPV VLP vaccines work so well?
- Antibodies (Abs): immune mediators of protection
- Consistency & durability of Ab responses to VLPs
- B cells recognize dense repetitive protein arrays
- VLPs have highly repetitive antigen displays
- Other advantages of VLPs
- One dose of Cervarix induces durable serum Abs
- HPV’s Achilles heel for prophylactic vaccines
- Antibody response in the cervix to IM injections
- In vivo murine model of vaginal HPV infection
- Antibody titers and protection
- Transfer of rabbit polyclonal anti-16L1 VLP sera
- Low levels of Abs prevent transfer to keratinocytes
- In vitro vs. in vivo protection of Gardasil sera
- Conclusions
- Key collaborators
Topics Covered
- Human papillomavirus (HPV) lifecycle
- Cervical HPV infection and progression to cancer
- Primary and secondary prevention method
- Prophylactic HPV vaccines
- Efficacy and durability of HPV viral-like particles (VPL) vaccines
- The potential of a one-dose vaccination program
- Randomized trials
- Vaccine protection against pre-malignant lesions
- Vaccine safety record & effectiveness
- HPV vaccine uptake
- Antibody response
- Increasing vaccine use
Links
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Talk Citation
Schiller, J. (2018, September 27). HPV vaccines to prevent cervical cancer and other HPV-associated diseases [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 26, 2024, from https://doi.org/10.69645/UYLZ7212.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. John Schiller has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Clinical Practice
Transcript
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0:00
Hello. My name is John Schiller.
I head the Center of Cancer Research at
the National Cancer Institute in Bethesda, Maryland, USA.
The title of my talk today is HPV Vaccines to Prevent
Cervical Cancer and Other HPV-associated Diseases.
It's a pleasure to be able to talk to you today about Prophylactic vaccines.
These vaccines have been widely touted as one of
the most significant advances in cancer prevention over the last two decades.
I hope to demonstrate in this lecture that these vaccines are
fortunate convergence of advances in basic molecular biology,
cancer etiology, and vaccinology.
Over much work remains before the full potential of these vaccines can be realized.
0:44
The outline of my talk is as follows.
We'll first of all start to talk a little bit about the basics
of HPV and its association with cancer and then
we'll move on to talk about the composition of the vaccines and
their efficacy and effectiveness in the actual immunization trials.
Then we'll talk about some of the implementation issues that remained to be resolved.
Finally, we'll get into more mechanistic studies where we
tried to figure out why they work so unexpectedly well.
1:13
So, HPVs are double-stranded circular DNA genome viruses.
Depicted here is the genome,
the two genes we're most concerned about are E6 and
E7 which are preferentially weakened and expressed in cancers,
and today, most of my talk will be about the virion proteins,
the major capsid protein which is L1 and the minor capsid protein which is called L2.
1:40
The virions are non-enveloped icosahedral shells which are
formed of 72 pentamers of these star-shaped L1s.
Overall size is 16 nanometers in diameter.
The second capsid protein, the L2,
is present at up to 72 copies,
they are shown here in red from an inside view and encapsulated within
this capsid which is 8kb circular double-stranded genome which is chromatinized.
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