Capsomere subunit vaccines could be the next-generation arsenal against Human Papillomavirus (HPV) that causes cervical cancer, a global meet discussing bench-to-bedside efforts for effective treatment of the scourge was told.
Speaking at an international symposium 'Human Papillomavirus-associated cancers: Translating research into cancer prevention and medicine' at Rajiv Gandhi Centre for Biotechnology (RGCB), Trivandrum recently, Robert L. Garcea from the University of Colorado said these protein subunits of the viral capsid have shown promise in leading towards an effective vaccine for cervical cancer. India contributes one-third of the global cervical cancer burden. "This would ideally suit the production of such vaccines and their use in developing countries like India", Dr Garcea said. The new immunogen is being produced for a phase I human trial, he said.
Laimonis A. Laimins from the Northwestern University of USA, elaborated upon caspase activation during terminal differentiation upon HPV infection. He proposed that the virions might be utilizing this activation in the host for propagation, thereby suggesting novel functions for proteins whose role have not earlier been reported in viral pathogenesis.
Rangaswamy Sankaranarayanan from the International Agency for Research on Cancer (IARC) in France, said his group was conducting a number of studies in developing countries demonstrating cost-effective strategies for HPV vaccination and testing.
The interesting link between HPV and HIV was brought forth when Priya Abraham from the Christian Medical College, Vellore, revealed the results of her study showing the higher risk among HIV positive women for HPV infection. Current vaccines may not be effective against high-risk HPV types seen amongst HIV positive women, she contented.
The meet extensively discussed the possibility of an HPV-specific targeted therapy. Elliot J. Androphy from the University of Massachusetts Medical School said the viral proteins E6 and E7 can be potential targets of antiviral therapy due to their role in the cell transformation pathways. He presented several promising leads from their high-throughput drug screening studies. Hiremagalur Jayaram from Indiana University School of Medicine, USA presented his team's studies on tiazofurin, which he proposed for the targeted lipososme-mediated drug delivery in the treatment of advanced cervical cancer. Bhudev Das from the Ambedkar Centre for Biomedical Research at University of Delhi elaborated upon several pharmacoderivatives with strong anti-HPV activity through molecular targeting of AP-1 (activator protein 1).
Nutritional anomalies and lifestyle patterns were also responsible in triggering infection and progression of HPV, the symposium was informed. Ashok C. Antony from the Indiana University School of Medicine said folate and Vitamin B12 deficiency promotes the amplification of HPV. Tobacco and alcohol use could worsen cases of HPV infection in the upper gastrointestinal tract, according to Dr Newell Johnson, Dean of Griffith University School of Dentistry and Oral Health, Australia. He also pointed out the need and merits of personalised medicine in cervical cancer treatment.
Lawrence Banks' group from International Centre for Genetic Engineering and Biotechnology, Italy, through their studies on the role of HPV E6 PDZ-domain interactions gave new insights into how the loss of cell polarity might lead to malignant progression. Massimo Tommasino of IARC, France presented his work on the role of E6 and E7 oncoproteins in inhibiting the transcription of genes involved in growth suppression and apoptosis. The concept of Notch signaling pathway in inducing enhanced tumorigenecity and stemness in human cervical cancer cells was introduced by Sudhir Krishna of the National Centre for Biological Sciences in Bangalore.
The immunology of tumor progression was also widely discussed. Margaret Stanley from the University of Cambridge elaborated upon the role of prophylactic vaccines that could circumvent the immune evasion strategies of the virus. Shubhada V. Chiplunkar from the Advanced Centre for Treatment, Research and Education in Cancer, Mumbai, discussed findings on the suppression of Natural killer cells (NKTs) by regulatory T cells (Tregs) thus enhancing tumor progression. She proposed an immunotherapeutic approach by manipulating Tregs and NKTs for the treatment of cervical cancer. Jayashree Subramanyam from Kidwai Memorial Institute of Oncology, Bangalore, put forward the concept that multi-step carcinogenesis results from cross-talk of cancer cell-intrinsic factors and host immune system effects.
Several novel methods for cervical cancer detection and analysis were also discussed during the meeting. Michael Pawlita from German Cancer Research Centre dwelled upon the application of versatile multiplex platforms developed by the centre in HPV genotyping and serotyping. Stephen Kam-Cheung Ng from Chinese University of Hong Kong elaborated on the higher sensitivity of liquid-based cytology for better sample preparation.
Neeta Singh from All India Institute of Medical Sciences, India, presented the results of an extensive study on E6/E7 and L1 mutations in cervical cancer isolates from different regions in India. Sharmila Sengupta from the Indian Statistical Institute also talked on her study on the genetic and epigenetic factors associated with HPV16 among Indian women. The relevance of HPV vaccine in the Indian scenario was laid out by Swati Bhave of the Indraprastha Apollo Hospital in New Delhi. Partha Basu from Chittaranjan National Cancer Institute in Kolkata elaborated upon the accuracy of real time detection to identify invasive cervical cancers by the typing of E6/E7 mRNA.
Various clinical trials involving prophylactic and quadrivalent HPV vaccines were dealt upon in detail by Suzanne Garland (University of Melbourne) and Gregg Sylvester (USA).
Convincing locals about the importance of screening for HPV has traditionally been a challenge in India. Patti Gravitt from John Hopkins Bloomberg School of Public Health discussed the problems they faced during an educational community programme in peri-urban villages of Hyderabad. She suggested effective ways of communicating the idea of prevention. Neerja Bhatla from AIIMS shared a community based success story where attempts at testing HPV 16/18 prophylactic vaccines had proved fruitful.
