Efficacy, safety, cost: India’s decade-old debate on the cervical cancer vaccine erupts again

The debate over the use of vaccines to prevent cervical cancer in India came to the fore again last week when the Ministry of Health and Family Welfare indicated that it was unlikely to include Human Papilloma Virus or HPV vaccines in the national immunisation programme.

The health ministry’s decision comes even though the National Technical Advisory Group on Immunisation is still considering the introduction of the vaccine into the programme. However, the Swadeshi Jagran Manch, an affiliate of the Rashtriya Swayamsevak Sangh, wrote to Prime Minister Narendra Modi in early December calling such a move an “unmitigated disaster” and asking for the vaccine to kept out of the public health programme.

A few days later, Dr Soumya Swaminathan, deputy director general of the World Health Organisation and former director general of the Indian Council of Medical Research, told The Indian Express that the vaccine should be introduced in India since it could help avert a large number of cervical cancer deaths in the country.

Cervical cancer is the second leading cause of cancer deaths among women in India. More than 122,000 women in India are diagnosed with cervical cancer and more than 67,000 die of the disease every year. About 25% of all cervical cancer deaths in the world occur in India.

The most common cause of cervical cancer is HPV. There are more than 100 types of the virus, of which at least 13 are known to cause cancer. Two strains – type 16 and type 18 – cause about 70% of all cervical cancer. This makes cervical cancer one of two vaccine-preventable cancers. The other is the cancer of liver – the Hepatitis B vaccine helps prevent it.

There are two kinds of cervical cancer vaccines currently widely available. Cervarix manufactured by GlaxoSmithKline is a bivalent vaccine that protects against infection by two HPV strains – type 16 and type 18. The other vaccine is Gardasil manufactured by Merck, which is a quadrivalent vaccine that provides protection against four HPV strains – types 16, 18, 6 and 11. Types 6 and 11 cause genital warts that are additional risk factors for cervical cancer. The vaccines are usually administered to girls and women between the ages of nine and 26. The vaccines do not treat pre-existing HPV infections and so must be administered before initiation of sexual activity.

India approved the two HPV vaccines in 2008 and they have been available in the private medical sector. However, the vaccines are expensive, priced at between Rs 2,000 and Rs 3,000 for a single dose. The vaccination consists of a series of two or three doses depending on age. The government has been considering introducing the vaccines into the public health programme, which would allow women and girls from poor households to access them. The government had tied up with the Global Alliance for Vaccines and Immunization to procure the vaccine at subsidised rates.

Among the many factors that are considered while introducing a vaccine into the public immunisation programme are vaccine efficacy, vaccine safety and how cost effective it is.

Efficacy

The efficacy of the HPV vaccine is measured as its ability to prevent HPV infection, genital warts and precancerous lesions. Recent reviews of how HPV vaccines have performed over the past decade show that the two vaccines have high efficacy, preventing infection and lesions for between five and 10 years after immunisation. However, the HPV vaccines are only a recent development and there is no long-term data available to indicate for how many years the vaccine will remain effective.

“The data will only start coming in when we are able to follow up with girls who have been vaccinated for 20, 30 or 40 years,” said Anant Bhan, researcher on bioethics, global health and policy. “So we need good post-marketing surveillance.”

Post-marketing surveillance is the practice of monitoring people who have received a drug, vaccine or medical device after it has passed clinical trials and has been approved by medical regulators for sale and use.

Being vaccinated does not guarantee protection against cervical cancer because the HPV strains that the available vaccines protect against are not the only strains that can cause cancer. Moreover, cervical cancer can also have other causes – smoking, for instance, is causally related to cervical cancer. Therefore, even women who have received the HPV vaccine need to be screened regularly for cervical cancer.

Safety

Concerns over safety of the HPV vaccine in India go back many years. In 2009, an HPV vaccine trial in Gujarat and Andhra Pradesh conducted by the Program for Appropriate Technology in Health, a non-profit organisation in the United States, came under scrutiny for endangering the lives of participants. The study involved vaccinating 13,000 girls in Andhra Pradesh and 10,000 girls in Gujarat aged 10–14. The government halted the trial in March 2010 after seven girls who had received the vaccines reportedly died during the trial. A government enquiry concluded that the deaths were unrelated to the vaccines. (One death was due to snakebite, one girl drowned and two committed suicide by ingesting poison.) A standing committee later concluded that the study violated ethical norms and India’s laws and regulations.

The Supreme Court is currently hearing a public interest litigation filed in 2012 raising questions about the trial and the vaccine.

“The vaccine by itself has had a historical safety issue in India with the whole problem with the clinical trials, which has affected public perception because there really has not been a resolution,” said Bhan.

While a number of public health groups have raised valid arguments for more rigorous testing of the vaccines for safety, the Swadeshi Jagran Manch’s letter to the Prime Minister is flawed in making this case. The letter says that a World Health Organisation report shows that HPV vaccines have the “highest rate of adverse effects among all vaccines in use” and cites a European study that looked at adverse events from HPV vaccinations. In fact, the study does not suggest that HPV vaccines have the highest rate of adverse events but says that the “reporting rate of serious reports with this combination of [adverse events] for HPV vaccines was 53.3 % and 43.9 % for other vaccines”. The study also says that a causal association of the adverse events with the HPV vaccine remains uncertain and has called for further investigation into the reports.

The WHO issued a safety update of HPV vaccines in July 2017, recording the findings of the Global Advisory Committee on Vaccine Safety that investigated reports of adverse events. The committee concluded that there is no evidence to suggest a causal association between HPV vaccine and and the neurological and chronic fatigue disorders.

At the same time, a recent investigation by Slate revealed problems with the clinical trials for Gardasil, which was supposed to establish the vaccine’s efficacy and safety before it was approved. The article also raises questions about why regulators knowingly accepted the company’s flawed data.

Cost-effectiveness

The more recent debate over the introduction of HPV vaccines into India’s public health programmes has centred around cost effectiveness. Delhi and Punjab have incorporated the HPV vaccine into their public health programmes. In May 2017, researchers from the the Post-Graduate Institute of Medical Education and Research published a paper in the journal Cancer claiming that the administering the HPV vaccine over one year had proved to be cost-effective. However, another group of researchers led by Dr Jacob Puliyel, head of paediatrics at St Stephens Hospital in Delhi and member of the National Technical Advisory Group on Immunisation, published a rebuttal saying that the PGIMER researchers had used a faulty model and that the HPV vaccine would not, in fact, be cost-effective in India.

“Given the poor quality and coverage of screening and non existent screening programmes in most states, the question is would be a priority for allocation of resources,” said Sarojini N, founder of the SAMA, a non-profit organisation that works on women’s health and one of the petitioners in the public interest litigation.

Other health activists believe that the vaccine should become part of the immunisation programme regardless of current costs.

“The cost of the vaccine will come down as soon as it is included in the national programme,” said Dr B Ekbal, public health activist and member of the Kerala State Planning Board in an email. “Even otherwise if a vaccine is useful the government should find resources for the expenses.”

Any vaccine has potential side effects. What many public health specialists are advocating is simply that before the vaccine is introduced, the immunisation programme establish efficient systems to pick up and report adverse events, provide treatment and compensation to those affected, and be ready to suspend the vaccine, if necessary. The government should also be transparent and share data on the basis of which it decides whether or not to use the vaccine.

Moreover, the HPV vaccine is only part of the strategy to bring down cervical cancer incidence and deaths. For instance, India still does not have adequate screening for cervical cancer. “The most important aspect is to emphasise screening programmes and early diagnosis which can bring down the cervical cancer rates,” said Sarojini of SAMA. . “Evidence so far from other countries’ experiences shows that cervical cancer rates and mortality rates have come down because of screening programmes. We need an efficient screening programme with quality health care infrastructure including trained health workers, availability of gynaecologists.”

Bhan believes that women’s health does not get enough policy attention. “Part of the problem is that women’s health has often been reduced to maternal health,” he pointed out. “But, especially in an aging population, we should be talking about health of women beyond reproductive health.”