Exclusive: Life beyond fear

By M H Ahssan

No parents would like to see their daughter suffering from painful cervical cancer that took away the life of Jade Goody. But, now protecting your little girl from cervical cancer is possible thanks to a vaccine and regular screening.

Prevention is better than cure, and when it is about reventing cancer, there is no thinking twice. Today there are therapies available for treating cancer, if detected at an early stage, but there are still many unanswered questions about this malignant neoplastic disease. Today thanks to Jade Goody, cervical cancer is well known as she came forward to show the plight of this terrible disease to whole world and since her public diagnosis there had been a vast awareness about cervical cancer among people across the world.

Even President Barack Obama's mother was a victim of cervical cancer. It is a disease that has always been prevalent but went blissfully unnoticed. Cervical cancer is one of around 200 different types of cancer and develops in the cervix, the cone-shaped part of the uterus that connects the upper part of the uterus (the womb) and the vagina. It is the second most common malignancy in women worldwide, and it remains a leading cause of cancer-related death for women in developing countries like India.

Rajani Bhisey, who has been a Senior Scientist and Head, Carcinogenesis Division in the Cancer Research Institute, Mumbai states that cervical cancer incidence varies across the world. Globally, new cervical cancer cases are diagnosed in about 500,000 women every year and annual death toll is more than 280,000. She informs, "Government of India has set up several cancer registries in the country to estimate the incidence of various types of cancers in different regions. According to these estimates, the number of new cervical cancer cases occurring each year varies from 18 to 30.6 per 100,000 female population, the overall incidence rate being 18.8 per 100,000 women. More than 70 percent of the cases report for diagnosis and treatment in the advanced stages of the disease leading to poor survival and high mortality rate."

Dr Gupta, Gentech Diagnostics, point outs that the World Health Organisation (WHO) or Globocan data shows that there are 131,000 new cases and 90,000 deaths due to cervical cancer. However in reality there are over 200,000 new cases and nearly 125,000 deaths due to this deadly disease. "Cancers do not have many therapeutics or preventive drugs, unfortunately the disease is discovered in the advanced stage primarily due to the lack of screening or voluntary diagnoses in India," Gupta avers. The most shocking fact is every year, 74118 deaths occur in India due to cervical cancer, accounting for 27 percent of deaths worldwide. To place it more aptly every eighth minute, an Indian woman is dying due to cervical cancer.

The culprit
All causes for cervical cancer development are not clearly understood, however, Human Papilloma Virus (HPV) infection is strongly associated with it. Of the more than 100 types of HPV, over 30 types can be passed from one person to another through sexual contact. Of these, infection with HPV type 16 and 18 is causally associated with cervical cancer. Dr Urvashi Prasad Jha, Senor Consultant Gynecologist, Gynae Laparoscopic & Onco Surgeon, Academic Co-ordinator, Department of Obstetrics & Gynaecology, Indraprastha Apollo Hospitals, informs, "There have been many theories on what causes cervical cancer. It was recently established that HPV virus plays a major role in almost all cases in causing cervical cancer. Different strains of HPV are associated for causing different cancers or other serious problems. More than 70 percent worldwide and 75 percent in India of cervical cancer is associated with HPV 16 and 18. Most genital warts are associated with HPV strains 6 and 11."

Speaking on the other factors leading to the cause of cervical cancer Bhisey, shares, "Besides HPV infection other factors such as first pregnancy at a young age, multiple child births, poor genital hygiene and unprotected sex with multiple partners are also known to increase the risk of cancer of the uterine cervix. Another life style factor associated with this cancer type is cigarette smoking. Women smokers are at twice the risk of developing cervical cancer in comparison to non-smokers. This disease develops in middle aged women who may harbor HPV infection and become susceptible to cancer development because of their life style."

Most HPV infections go away without any treatment over the course of a few years. However, HPV infection sometimes persists for many years, with or without causing detectable cell abnormalities. Dr Naveen A Rao, Managing Director, Merck Sharp & Dohme (MSD) India informs that "Cervical cancer is the most horrible painful disease that women can ever get. Any women can get infected of this life threatening disease in an early age and by the age of 40 die. The symptoms of this life threatening disease are bleeding with pain, vaginal discharge, pain during sex etc. If detected in time the cancer can be treated, but the irony is that by the time a patient gets to notice these symptoms it is too late for the patient to turn back."

Diagnosis
Cervical is one among the few cancers that go through pre-cancerous stage and with timely detection one can avert it from developing into cancer and for this frequent screening is a must. The Pap test also called as Pap smear is a way by which cervical cancer can be detected. It is a simple test--usually conducted in a doctor's office or clinic - that detects abnormal or cancerous cervical cells. In India effective coverage i.e. proportion of eligible women who report that they have had a pelvic exam and Pap smear in the past years for cervical cancer screening is very low.

Jha informs, "Apart from Pap smear test there is also a test called as HPV testing where you can test for HPV virus directly and can even identify the high risk virus and type the virus. These types of test are now available in India example, Dr Dangs Lab owned by Dr Navin Dang. They do the HPV typing in India."

Dr C N Purandare, President, The Federation of Obstetric & Gynaecological Societies of India (FOGSI), avers, "Screening is an absolute necessity to avoid reaching the state where the problem can become major and incurable later. However, Pap smear tests in such a large population is not possible. Woman in India need to understand that they have to undergo regular gynaecological check ups irrespective of the fact that they have a major problem or whether they are pregnant or not."

Pap test is helpful as it can detect cervical changes before they progress to cancer; it is credited with significantly reducing cervical cancer deaths since its widespread use began in the 1950s. However, like other medical tests even Pap tests are not foolproof. Sometimes they do not find cervical abnormalities that actually exist - but regular screening can help women and their healthcare providers overcome these false-negative screenings. This is where the role of preventive measures comes into picture and the vaccines act as a catalyst against HPV.

Valuable vaccines
Availability of prophylactic vaccine has made it possible to control cervical cancer more successfully. Efforts for preparing a vaccine against HPV began in mid 1980s and the scientists at George Town Medical Center, the University of Rochester, the University of Queensland in Australia, and the US National Cancer Institute developed the vaccine. Today, two brands of cervical cancer vaccine are available in the Indian market; MSD's cervical cancer vaccine, Gardasil launched in October 2008 and GlaxoSmithKline's (GSK's) Cerverix launched early this year.

These vaccine has a very simple modus operandi. They are made from hollow virus like particles assembled from recombinant HPV coat proteins. When injected into, they produce antibodies which can neutralise the infecting viruses. Bhisey informs, "If an exposure occurs, the vaccinated person's antibodies interact with the L1 protein coat of the virus and prevent viral infection that is integration of viral DNA into the cellular genome. Vaccinations thus prepare immune cells to ward off future infection by high-risk HPV viruses targeted by the vaccine."

Gardasil is the only quadrivalent vaccine that helps protect against four types (types 6, 11, 16, 18) of HPV. Apart from cervical cancer this vaccine also helps in preventing diseases such as abnormal and precancerous cervical lesions, vaginal lesions, vulvar lesions; and genital warts, caused by these types of HPV. Gardasil is recommended to be given to females aged between nine to 26 years and is given as three injections over a period of six months; After the first dose is given, it is followed by another dose two months later, and the third and last dose, six months after the first dose.

Whereas, its contender Glaxo's Cerverix is approved for use in females aged 10 to 45 years old to protect against two dangerous cancer strains of HPV types 16 and 18. It is the only cervical cancer vaccine that has been formulated using the innovative adjuvant system, called AS04. It is administered in a three dose schedule required to given at zero, one and six months. Both the vaccines are administered intramuscularly in the upper arm or thigh.

Speaking about the benefits of these vaccines, Jha informs, "These vaccines act as primary prevention before the infection happens. Thus it's logical that it should be taken in an early age as it boosts immune system more effectively as immune system becomes a little less active as a person gets older. Ideally this vaccine should be taken before any first sexual intercourse so that the vaccine could be more effective. That is why it is always best to give HPV vaccine to girl at a young age preferably by nine."

Affordability vs risk
Availability of the vaccine is not the only issue; accessibility and price also matters as it plays a vital role in providing the product to the end user. Right now the price of the vaccine is priced higher; since each technology has a price, a price of innovation, R&D, and efforts to bring to the masses. MSD's Gardasil is priced around Rs 2,800 per dose, whereas, GSK's Cerverix is priced at around Rs 3,300 each dose. So, it costs around Rs10, 000 for recommended three shots.

Jha feels, "Price of the vaccine is certainly out of reach for some people but when we come to think about it, treating cervical cancer would be more expensive than preventing it by way of vaccination and frequent screening, the choice is on us."

Agreeing on the same, Supratim Majumdar, Industry Analyst, South Asia & Middle East, Healthcare, Frost & Sullivan informs, "Prices are beyond the reach of common Indian populace which would restrict them from vaccinating young girls and providing protection against cervical cancer, the second commonest major cancer in women. Increasing awareness and consequent rise in demand; and competition would bring down the prices but affordability is still going to remain more or less same." However he goes on to say, "Initiatives and funding support of supra-national agencies and the government could help in making cervical cancer vaccination affordable and accessible. Support from vaccine marketers has got a key role in successful implementation of such initiatives."

When weighed against life, the price of the vaccine certainly seems less since shedding a few thousands seems more affordable than losing life. As Dr Shailesh Mehta, Medical Director, Clinical R&D, Medical Affairs Biologicals South Asia, GSK justifies, "The price of the vaccine is not an issue compared to the role it plays in keeping the deadly disease at bay. Price will come down as the usage increases. Cervical cancer is a social problem and this has to be dealt with on a united front."

At present more importance should be given in eradicating the disease by proper education on it and by providing available preventive remedy to the women in India since these vaccines are a solution to a massive problem in India. Affordability could be understood later since it depends upon the market and acceptability. The problem of affordability will be solved as soon as the market rises.

Other factor that can help reduce price is by way of increased competition. There should be indication from the generic companies too so that the problem of cervical cancer can be tackled more strategically with affordability. Domestic vaccine manufacturers have already initiated the process of developing indigenous cervical cancer vaccines that would be more efficacious and affordable. Sharing on the same Majumdar informs, "Hyderabad based Shantha Biotech has started working in this regard. Serum Institute is also doing research to develop cervical cancer vaccine. Emcure's biotech-arm Gennova Biopharmaceuticals have partnered with Tata Memorial's research satellite Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) to develop cervical cancer vaccines. Some of these initiatives, if successful, are expected to take few more years to develop and commercialise vaccines. Nevertheless, it will drastically bring down prices of these vaccines."

Government initiatives
Nothing can be done without the support and collaboration of the government. Active government participation and help can deal with many problems like awareness, affordability, availability etc.

According to Majumdar Indian Council for Medical Research (ICMR) has joined hand with MSD Pharma under a public private partnership (PPP) programme for a long-term study on the feasibility of the cervical cancer vaccine for a possible universal vaccination programme in the country. Similarly Department of Biotechnology has sponsored two studies of Emcure for development of cervical cancer vaccine. "More such initiatives are needed from different governmental agencies and institute to support the R&D initiatives of domestic companies to develop such vaccines. Different PPP schemes for funding R&D can be utilised by domestic companies to achieve their R&D goals," feels Majumdar

Public private partnership (PPP) is very essential not only for pricing but also for a host of other reasons. Rao insists, "Everything is not always money. What we need is a better understanding between the pharma companies, the doctor community (so that they create the necessary awareness about the disease) and the government, so that they can provide the infrastructure, logistics and other necessary needs to make it available to each and every woman of the country. It has to be joint effort between each of us."

Eradication through education
Mothers need to be educated about the importance of vaccinating their girl child against cervical cancer. These vaccines should be projected as a cancer preventive vaccine rather than only HPV preventive vaccine as there can be social stigma attached to it if propagated only as HPV vaccine. In fact, there is opposition to including it in the national vaccination programme as some would see it as encouraging promiscuity by giving protection from a disease/infection associated with having multiple sexual partners. Therefore mothers should be given guidance and educated on the pros of vaccinating their girl child and protecting them in future.

Purandare asserts "The usefulness of the vaccines has to be conveyed to them as this would certainly help in bringing the burden of disease down. But at FOGSI we also try to propagate the importance of PAP smear test and that it should not be seen just as a once in a life time test, but a much needed regular health check up. PAP smear test is a must irrespective of vaccination, however, disease burden, high mortality rate, and lack of good quality PAP smear testing facility has prompted for urgent need of vaccination."

More over it would be great if these vaccines are included in the immunisation programme as this would not only help in reducing the price of the vaccine but also the disease burden. Rao asserts, "As a company we would say we have succeeded in our aim of eliminating cervical cancer only when this vaccine is accessible to women living in the remotest village of the country. And in order to achieve this we need the help of the government. In this case what we are preventing is cancer and not a disease like malaria, measles etc; we need to put that in perspective. In some countries like Australia, US, the use of this vaccine has been made mandatory insisting the use of vaccine on all young girls of these countries. It should also be followed in India as well."

Vaccines have certainly made the future more secure for women around the world by enhancing immunity and making viral elimination far sure. However that should not stop a woman from routine screening since there is no hardcore evidence to prove how long this immunity would stay and would it require another booster after 10 to 12 yrs etc. So the best way to keep cervical cancer at bay is by administering the vaccines to a girl child as early as possible and then by undergoing screening at frequent intervals. It is important to note that regular Pap smears are still required for women who choose vaccination as the vaccine does not provide complete protection against all cervical cancers.

For all this the government needs to take required initiatives by providing proper screening facilities and funding for detecting and eradicating this deadly disease. As Gupta, rightly puts in, "The cervical cancer can be best prevented by screening women above 30 at least every five years if not earlier. We have nearly 150 million target women in India who are at highest risk due to this cancer. We need our district level healthcare centres be equipped with screening methods and primary health care centres at the village level be trained to enhance awareness, bring these women once in five years to district level hospitals and do screen-test in one or two visits. Many complex problems have a simple solution; one needs an eye to see this, and like-minded administrative machinery to support it."

To put it in simple words cervical cancer is major problem that needs urgent attention; thankfully with the help of vaccines and proper screening it can easily be brought under control. But what is needed is a proactive steps not only by the government agencies, pharma companies and doctors but also needs active collaboration and support from the people as it is a problem affecting us and only we can stop it.