A disease which kills almost 300,000 women a year – including 67,500 women in India – could be all but eliminated by the end of the century if efforts are made to increase access to a lifesaving vaccine according to recent research published in The Lancet.
The disease is cervical cancer. The vaccine is against the human papillomavirus (HPV).
Cervical cancer is one of the leading threats to women’s health, both in India and worldwide. Cervical cancer kills one Indian woman every eight minutes, making the disease one of the country’s most lethal cancers. Worldwide, it accounts for the second highest number of cancer-related deaths.
The potential benefits of immunising more women against the disease has been highlighted in the research reported in the Lancet. Between 2020 and 2069, failure to expand HPV immunisation will result in 44.4 million cervical cancer diagnoses. The majority of these will be in low and middle-income countries like India.
On the other hand, expanding prevention programmes such as vaccination against HPV in the next few years could avert thirteen million cervical cancer deaths. Moving towards HPV vaccine coverage of 80-100 percent within the next few decades has the potential to drive down cervical cancer rates to the extent that the disease would almost disappear as a public health threat by the end of the century – even in countries towards the bottom of the Human Development Index (HDI). In the process, millions of cancer cases and lives would be saved.
India had more cervical cancer cases and deaths than any other country. It accounts for a quarter of cervical cancer-related deaths worldwide. Yet despite this, uptake of a vaccine which could prevent cases of the disease in staggering numbers continues to stall in India. The story as to why has played out largely behind the scenes, apparently involving oftentimes deliberate efforts by lawmakers, lawyers and political influencers.
There is a well-established link between cervical cancer and infection with the human papillomavirus (HPV). Of the more than 150 HPV strains, experts believe two – HPV types 16 and 18 – to be responsible for seventy percent of cervical cancer cases. On top of cervical cancer, infection with various different strains of HPV can also be linked to cancers of the anus, penis, vulva, vagina, mouth, and throat.
Researchers estimate that use of a new HPV vaccine that protects against nine strains of the virus could prevent ninety percent of HPV-related cancers worldwide. The nonavalent HPV vaccine targets seven strains of the virus linked to cancer cases in men and women alike including HPV16 and HPV18.
Consequently, vaccination against HPV could prevent a significant portion of cancer cases in India. According to one estimate, India could prevent 70,000 deaths related to cervical cancer alone every year by scaling up HPV vaccination.
The findings published in The Lancet magnify what is already a clear consensus. The HPV vaccine is effective as a protective measure against cancer cases. Cervical cancer especially would be mitigated. Despite this, the HPV vaccine has not been included in India’s Universal Immunisation Programme (UIP) until now. Efforts to do so have been recommended by public health experts and even the Centre’s own technical advisory body on immunisation.
This report aims to explore the reasons why.
A human trial and ethical violations?
In 2009, a feasibility study of use of the HPV vaccine was conducted in Andhra Pradesh and Gujarat. Over the course of the study, three doses of the vaccine – provided by GlaxoSmithKline and Merck – were administered to 23,500 participants. Of these, the majority were girls aged nine to fourteen, recruited from tribal areas of the states. In the aftermath, seven deaths of participants in the research were reported. The furore following the study was of a magnitude rarely seen in public health scandals in India.
The studies were a collaborative effort. Global NGO PATH, with funding from the Bill and Melinda Gates Foundation, carried out the research. They receive technical assistance from the Indian Council of Medical Research (ICMR) and local health authorities. The role of each actor in the research was heavily scrutinised following reports of deaths of participants, which prompted the Centre to abort them in 2010.
Criticism came hard and fast from government bodies. A committee investigating the incident strongly criticised PATH for purported ethical violations. They stated that government institutions which provided technical support – particularly ICMR representatives – exhibited “serious dereliction of duty…apparently [acting] at the behest of the PATH in promoting the interests of manufacturers of the HPV Vaccine.”
Ethical violations reportedly related to the involvement of minors in the research, from whom consent may not properly have been acquired. This is despite the ICMR giving ethics approval to PATH in advance of the study.
One allegation made against PATH concerned the nature of informed consent acquired during the course of the study. An investigative report by women’s health group SAMA into one of the study’s sites in Andhra Pradesh alleged that participants were provided “consent forms…in English which even the health care provider administering the vaccine to them may not be able to read, let alone the participants.”
PATH maintains that their conduct in Andhra Pradesh and Gujarat did not amount to ethical violations as they were post-licensure observational studies, as opposed to clinical trials. PATH insist that clinical trials had been performed in advanced of the studies, as was a condition of the licensure to conduct them.
“Post-licensure observational studies in Andhra Pradesh and Gujarat do not seek to evaluate the efficacy or safety of these licensed, approved HPV vaccines,” PATH asserted at the time. They added that “the safety and efficacy of these vaccines have been documented in numerous studies and endorsed by numerous international and national regulatory agencies.”
Dr Christopher Elias, then-chief executive officer and president of PATH, maintained that “PATH and its Indian collaborators worked with two ethical review committees in India and one in the United States to design study protocols and informed consent materials. PATH is confident that these procedural safeguards informed and guided all aspects of study implementation and conduct.”
In the years since the HPV study, guidelines for the participation of minors in clinical research in India have been issued by the ICMR. Such rules could prevent any legal ambiguity which might have engendered the situation surrounding the HPV vaccine study. There has also been expressed hope that the guidelines could avert demonisation of all clinical research – a vital part of biomedical research.
As Health Issues India itself has reported, clinical trials do incur a human cost. As the number of clinical trials conducted in India increase, the need for transparency and accountability in the conduct of such research is of paramount importance. Since 2015, at least 1,100 participants in clinical trials in India have died. However, it is important to note that of these deaths, only 88 have been definitively linked to adverse effects arising from the trials themselves.
The distinction here is important, especially when talking about the case of the study run by PATH. While the seven fatalities mentioned above did occur, they were not the result of the HPV vaccine studies themselves. This much was established by government-run investigative committees.
Of the seven deaths reported, five were patently unrelated to the study
- One was the result of a drowning incident in a quarry
- One was the result of a snakebite
- Two were the result of pesticide inhalation
- One was due to complications from malaria
Of the remaining deaths, one of the girls suffered a high fever and the other experienced a suspected cerebral haemorrhage (stroke). Yet as investigative committees established, the likelihood of either of these cases being related to the vaccine administered over the course of the research was slim.
What can be drawn from the furore after the study goes far beyond perceived ethical violations in the conduct of the actors involved. Much of the tone of the coverage since has constituted an unwarranted and scientifically unfounded demonisation of the HPV vaccine.
“Unproven and hazardous”
The Human Rights Law Network, as an example, described the vaccines used in the trial as “unproven and hazardous”. This was in a document published in May last year. The HRLN utilised the same argument in a writ petition to the Supreme Court filed in 2013.
Yet earlier that year, in February, the Reproductive Health Initiative (RHI) – an arm of the HRLN – republished a Scroll.in report claiming clearly that “the deaths were unrelated to the vaccines.” In the document, bioethics researcher Anant Bhan was quoted as stating ““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.”
What certainly has not helped is the use of language such as “unproven and hazardous” in legal documents to describe vaccines where safety is not in doubt and efficacy is supported by health researchers. The use of such language has lent credence to the anti-vaccination movement, who continue to recycle myths concerning the HPV vaccine study in India as a means of challenging use of the HPV vaccine itself.
A flawed case against the HPV vaccine
Perhaps the most concerning manifestation of how these myths have undermined the use of the HPV vaccine is seen in their effect on government policy. When the National Technical Advisory Group on Immunisation (NTAGI) recommended the HPV vaccine’s inclusion in the UIP, it took only a letter from a national co-convener of the Swadeshi Jagaran Manch (SJM) to the Prime Minister to discourage the Centre from doing so. Even as the matter was still under consideration of the NTAGI, the Centre had reportedly committed itself to shelving the vaccine regardless of the NTAGI’s decision.
The letter from the SJM regurgitated myths about the safety and efficacy of the HPV vaccine. This marked a clear indication that, despite consensus it was not the HPV vaccine that caused deaths in Andhra Pradesh and Gujarat in 2009, the ghost of the incident will overhang efforts to expand access to the HPV vaccine in India for some time.
Among critics of the SJM’s letter was the Scroll.in report circulated by the HRLN.
“The Swadeshi Jagran Manch’s letter to the Prime Minister is flawed in making this case,” the report notes. They noted that data from the WHO was misrepresented to claim a high rate of adverse effects associated with the HPV vaccine.
It would be the same year as they reprinted the Scroll.in report that the HRLN again wrote that the HPV vaccines used in the trial are “hazardous”. It would be the same year also that thousands of Indian women would lose their lives in cervical cancer. In years to come, thousands more are likely to succumb to the same fate if the HPV vaccine is not rolled out as part of the UIP.
Alleged ethical violations linked to the study do not impugn upon the safety of the HPV vaccine. Yet stakeholders have used it as a pretext upon which to besmirch in efforts to make cases against NGOs and government bodies when the safety of the vaccine should not have been in question. In the process, efforts to roll out a life-saving vaccine addressing one of the biggest threats to women’s health in India have been impeded.