One of the recent concerns regarding the field of oncology is the increasing number of women who are being diagnosed with cervical cancer. India has the highest number of cervical cancer in the world, according to the International Agency for Research on Cancer (IARC), a part of the World Health Organization (WHO). Every year, approximately 74,000 patients die in the country out of 1,32,000 women diagnosed with this deadly disease. It is estimated that the number of cervical cancer deaths in women in India is likely to rise to 79,000 by the year 2010. Worldwide, around 2,80,000 women die of this disease every year and 27% of this burden is shared by India. The virus called Human Papillomavirus (HPV) causes the cervical cancer. This virus gets transmitted through sexual contact and even preventive measures like contraceptives cannot prevent it from entering a woman’s body. From infection, the virus takes 15-20 years to develop and attack as cervical cancer in a woman’s body. To prevent this, the vaccine should be administered from the age of 9-26 years, so by the time a girl reaches her late 40s she is safeguarded. The cervical cancer vaccine (also called the Human Papillomavirus or HPV vaccine) protects against the virus that causes almost all cervical cancers. Despite the availability of a preventive vaccine, cervical cancer has emerged the biggest killer of Indian women as every seven minute a woman dies of it.
The pharma majors, Merck and GSK have marketed the vaccines Gardasil and Cervarix respectively in the foreign countries. In USA the vaccination of the girl before school admission is to be made must legally in the coming days. But these vaccines are still not available in Indian market, though the number of patients is high. The Govt of India is tying up with a multinational company to bring a cost effective vaccine that is expected to combat cervical cancer. The Indian Council of Medical Research (ICMR) has already started mobilizing things to implement the plan in association with Merck which has produced the vaccine. The ICMR is there to establish an association with Lyon-based International Agency for Research in Cancer (IARC), which would bring a lot of investment to India.
Globally, cervical cancer is the second most common cause of cancer death in women. The cervical cancer vaccine can save lives, and prevent the fear and the costs related to cervical cancer and abnormal Pap tests. In India, cervical cancer vaccines are being highly promoted by both MSD and GSK. MSD launched Gardasil in India, late 2008 and GSK launched Cervarix locally in early 2009.
In October 2009, Inovio Biomedical Corporation, a leader in DNA vaccine designing, development and delivery, announced the interim safety and immunogenicity data from its therapeutic cervical cancer vaccine (VGX-3100) trial. VGX-3100 is a DNA vaccine targeting the E6 and E7 proteins of human papillomavirus (HPV) types 16 and 18 and is delivered via in vivo electroporation. It was found that the vaccine was generally safe and well tolerated, and achieved significant cellular and humoral immune responses at the lowest dose administered. Phase I clinical trial was designed to test the safety and immunogenicity of VGX-3100 in women with a previous history of cervical intraepithelial neoplasia (CIN) 2/3, a precursor lesion prior to the development of cancer. The immunization regimen consists of each subject receiving three immunizations at the indicated dose. The vaccine is delivered using Inovio's proprietary Cellectra intramuscular electroporation delivery device. The interim safety analysis indicated that all six subjects tolerated the vaccine administration and electroporation procedure well over each of the three vaccinations. The reported adverse events and injection site reactions were mild to moderate and required no treatment.
Although preventive vaccines have demonstrated efficacy in preventing HPV infection, they have shown no benefit in controlling cervical cancer in women already infected with HPV. A therapeutic vaccine capable of mobilizing the immune system to kill pre-cancerous and cancerous cervical cells would be a significant accomplishment and of great importance to the millions of individuals already infected with HPV. Inovio selected this important disease as its lead cancer target for its novel synthetic consensus SynCon DNA vaccines.
Presently, the VGX-3100 clinical trial is enrolling the second cohort of patients. Inovio is highly expecting full enrollment of all three cohorts in the first half of 2010 and full analysis of immunogenicity and safety data by third quarter of the year 2010.
Cervical cancer vaccines in India
Gardasil of Merck and Cervarix of GSK are the two vaccines which are available in the market. In India, cervical cancer vaccines are being actively promoted by both MSD and GSK.
Both of these vaccines aim two types (16 and 18) of HPV causing nearly 70 per cent of cervical cancers, with an efficacy of about 98 per cent. But Gardasil has an edge over Cervarix it blocks two other types (6 and 11) of HPV responsible for approximately 90 per cent of genital warts. Both of these vaccines Gardasil and Cervarix have WHO pre-qualification. WHO pre-qualification means that Gardasil is now eligible for procurement by the UNICEF and other UN agencies including the Pan American Health Organization (PAHO), for use in national immunization programmes.
During October 2009, the US FDA has approved Cervarix [human papillomavirus bivalent (types 16 and 18) vaccine, recombinant] produced by GSK for the prevention of cervical pre-cancers and cervical cancer associated with oncogenic HPV types 16 and 18 for use in girls and young women (aged 10-25). The FDA's approval of Cervarix was based on data from clinical trials in more than 30 countries involving a diverse population of nearly 30,000 girls and young women receiving Cervarix.
Cervarix was shown to be 93% efficacious in the prevention of cervical pre-cancers associated with HPV 16 or 18, in women without evidence of current infection with, or prior exposure to, the same HPV type at the time of vaccination. The majority (approximately 75%) of cervical cancers in North America are caused by HPV types 16 and 18.
Cervarix does not protect against disease caused by all HPV types. Till today, approximately 100 types of HPV have been identified, and of these, approximately 15 virus types are known to cause cervical cancer.
Cervarix has a clinically acceptable safety profile. The most common local adverse reactions and general adverse events in =20% of clinical trial participants were pain, redness and swelling at the injection site, fatigue, headache, joint and muscle aching, and gastrointestinal symptoms.
Merck Sharp & Dohme, a wholly-owned subsidiary of US-based Merck & Co, has revised the labelling on its cervical cancer vaccine Gardasil. The revised label will be informing patients on adverse events including fainting and seizure-like activity seen in some vaccination cases.
The cost of vaccination for cervical cancer is very expensive in India. Its price needs to be drastically reduced, especially in countries like India, where the risk of this disease is threatening. More number of companies should come up and they must make the price of this vaccine still more affordable for common people. In India, only two private companies are dealers of the vaccine which cost Rs 9,000 for three doses over a period of 6 months. Cervical cancer is the second most fatal form of cancer worldwide after breast cancer, and now it is soon turning to be the first major concern. Unless preventive measures are implemented soon, more than one million new cervical cancer cases would be diagnosed every year globally.
(The author is team lead, TCS, Mumbai)