The Dark Side of HPV Vaccines

R217m suspect vaccine dump

Race-based medicine is a discussion many scientists like to avoid, even though there’s consensus that race and ethnicity count in the distribution of infectious diseases. Photo credit: Harry Cabluck/AP

In Brief

  • Human papillomavirus (HPV) immunisation programmes are gaining traction in Africa, as pressure mounts on policy makers to accept the vaccines that are now controversial in many developing countries
  • The two vaccines marketed by US and UK pharmaceutical companies are believed to disrupt the link between HPV, a sexually transmitted virus, and cervical cancer
  • More women in sub-Saharan Africa are increasingly dying of cervical cancer – the school-based HPV programmes being rolled out in Kenya, Rwanda and South Africa target girls from 9 years of age
  • One study found the two “high-risk” strains protected against by the vaccines are more frequent in white women, and prompted a call for development of new vaccines aimed at the previously excluded strains in other race groups
  • Various interest groups continue to highlight the vaccine’s adverse effects, with one researcher involved in the trials of Gardasil saying the public deserves complete information on the risks and benefits, and the fact that the vaccine is not effective beyond five years
  • Should reported cases of grave side effects be ignored?

Of all scientific inventions for women’s preventative health, the vaccine against certain types of human papillomavirus (HPV) is considered the most ‘progressive’.

Invented in 1992 by celebrated immunologist, Professor Ian Frazer and Dr Jian Zhou at the University of Queensland in Australia, the vaccine is believed to disrupt the link between HPV  - a sexually transmitted virus infecting the skin and mucosal tissues - and cervical cancer.

With over 170 known types, HPV infection is extremely common in both men and women. 40 of the 170 types have been linked to sexually transmitted cancers: about 40% of vulvar, 60% of vaginal and 80% of anal cancers, and also genital warts, according to the International Journal of Cancer. A lot of people catch the virus within three years of becoming sexually active. The good news is that the infection clears up in 98% of cases, and one may never even know they were ever infected. However, the remaining 2% of infected persons are at great risk of getting cancer.

One way of screening for persistent HPV infection is through pap smears, but this option hasn’t been practical especially in developing countries. The objective of Frazer and Zhou’s invention (that was registered under US Patent No. 7,476,389), was to prevent the infection from happening at all, thereby reducing the risk of cervical cancer.

Two vaccines – Gardasil by US pharmaceutical company, Merck & Co and Cervarix by British company, GlaxoSmithkline – have been marketed since 2006 and 2007 respectively. The vaccines, which have been administered to more than 125 million people in 120 countries, are recommended by WHO for females from the age of  nine to 25.

In 2013, total worldwide sales of Gardasil were estimated at US$1.83 billion and Cervarix about 500 million Euros. The three doses of the vaccines (2 doses in some countries) are expensive, at more than US$100 in wealthy countries, but the subsidised deals offered by organisations such as GAVI Alliance have helped immunisation programmes to gain traction in developing countries. For the 2013-2017 period, the GAVI Alliance plans to purchase HPV vaccines from Merck &Co at US$4.50 per dose and US$4.60 per dose from GlaxoSmithKline, with Merck promising to further lower prices if GAVI purchases more of the vaccine in the future.

The Biovac Institute, which is contracted by South Africa’s government to supply GSK’s Cervarix,  is charging nearly double what GAVI pays, at $8.17.

Uptake appears strong in many parts of the world despite the reported adverse effects and slump in sales in the US, as big pharmaceutical lobbyists mount pressure on policy makers to accept the vaccines.

In sub-Saharan Africa where more women are now dying of cervical cancer, at least five countries - Ghana, Tanzania, Kenya, Cameroon, Uganda and Lesotho – piloted HPV immunisation programmes for adolescent girls. 

Rwanda, Kenya and South Africa are already rolling out national programs.

In South Africa, cervical cancer is the second most common cancer among women, and the most frequent cancer among women between 15 and 44 years of age. Of the estimated 7,700 women diagnosed every year, more than half will ultimately die of the disease. The high mortality rate is due to low screening coverage, late diagnosis and the effect of HIV/AIDs.

The Department of Health launched a government-funded school-based HPV vaccination program in April 2014. The program targeted over half a million girls in South Africa’s public schools aged 9 to 12 years. Eligible girls get two doses of Cervarix, which The Biovac Institute is supplying to the department at a total cost of R217, 200,000.

In two to four decades the maximum impact of the 2014 rollout will be known. Will the vaccination have prevented at least 70% of all cases of cervical cancers? We would hope so, but only if other interventions are implemented to ensure that women are continually screened since there is some confusion about the effectiveness of the vaccine beyond five years. Also, if you are black you might not be as protected: Gardasil and Cervarix vaccines do not target the strains of HPV that are most common in non-white women, according to American researchers.

The 170 types (strains) are generally sorted into “high-risk” and “low-risk”, with the former usually developing into cancer. In 1984 German virologist Herald Zur Hausen identified strains 16 and 18 as the main causes behind more than 70% of all cervical cancers.

A 2013 study conducted by Duke University Medical School says the two “high-risk” strains (16 and 18) that the vaccines protect against are more frequent in white women other than another races.

The findings by researchers led by Dr. Catherine Hoyo, associate professor of Obstetrics and Gynecology, explained why more Black and Spanish American women were more likely to contract HPV and die of cervical cancer than white women, despite the fact that they tend to get screened for cancer more regularly.

According to the study by Dr. Hoyo and colleagues, if a physician is looking out for 16 and 18, which are responsible for most cervical cancer, some cases might be missed because it seems like they are half as common.

In the American population, women most often get HPV strains 16, 18, 56, 39, and 66, while black women most often contract HPV strains 33, 35, 58 and 68. So, even though white women are not protected from all strains by the HPV vaccine, they are in a much safer position.

In Africa, data on HPV genotypes is limited, but the hierarchy of the types causing infections differ across the continent, according to a study conducted in 2008 titled Cervical Human Papillomavirus (HPV) Infection in South African Women: Implications for HPV Screening and Vaccine Strategies. HPV 35 dominated, together with HPV 16, followed by HPV 31, 45, 56 and 58.

The bottom line is, according to Professor Hoyo, new vaccines that can benefit black women need to be developed.

Merck, while responding to the Hoyo study argued that 16 and 18 strains are responsible for 70% of all HPV-related cancers. But, Professor Hoyo insisted more strains are involved.

Race-based medicine is a discussion many scientists like to avoid, even though there’s some consensus that race and ethnicity matter in the distribution of infectious diseases. It is a contentious issue mostly because race-based medicine is based on genetic factors far more complicated than just skin color. Additionally, claiming that different races require different medical care is surprisingly politically incorrect; it is assumed such exploration can deepen racial divides.

As professionals bicker about racial profiling in HPV, more people are getting infected with HPV and cervical cancer. Meanwhile, the pharmaceutical industry is ready to make a killing selling treatment drugs.

A new HPV vaccine that targets HPV types 31, 33, 45, 52, 58, 6, 11, 16 and 18 is under production for the US market. 33 and 58 strains are most commonly found in black American women.

The reported side effects cannot be overlooked. In March Denmark’s public broadcaster TV2 aired the documentary, The Vaccinated Girls – Sick and Betrayed, that exposed the side effects of the vaccines. Another study published in April by researchers at the University of Texas Medical Branch found women who receive the HPV vaccine are more at risk of being infected with certain high-risk strains of the virus than women who don’t get the vaccine.

As reported by UK-based The Healthier Life, the general public is being denied crucial information that could enable informed decisions.

In the US the Vaccine Adverse Events Reporting System (VAERS) – a voluntary reporting system with limitations including verification that the reported effects are actually caused by the vaccine - continues to receive reports of side effects following vaccination with Gardasil. While many of the reported adverse reactions are mild, for example headaches and nausea, there are severe reactions including thrombosis, pancreatitis, anaphylactic shock, Guillain-Barré syndrome and also some fatal cases. Similarly, adverse reactions have been reported in the UK where Cervarix is used, as well as in other countries.

Good vaccines do have side effects, but when credible sources including doctors, researchers, and vaccine safety advocates raise alarms and call for further work, shouldn’t authorities pause like Japan’s government did in 2013 when it withdrew recommendation for the HPV shot after side effects were reported?

In South Africa’s Western Cape Province some parents reportedly declined to give consent for the vaccine citing adverse effects.

The European Medicines Agency, which makes recommendations to the European Union about the safety of drugs, announced in July that it had begun to review HPV vaccines to “clarify aspects of their safety profile”.

Dr. Diane Harper, who has researched HPV extensively and helped Merck carry out the safety and effectiveness studies that got Gardasil approved, spoke out about risks and benefits of HPV vaccines, saying young girls and parents need more complete warnings before receiving the vaccine to prevent cervical cancer. Also, there’s no proof that the vaccine is effective beyond five years, she said.

While most people are in agreement that the theory behind the vaccine is sound, in practice the issue is more complex and the gaps in knowledge need to be filled, opines Dr Charlotte Haug, the editor-in-chief of The Journal of the Norwegian Medical Association.

“When you suppress a few strains of a virus, as the vaccine does, other strains become dominant and take their place. Nature never leaves a void, so if HPV 16 and HPV18 are suppressed by an effective vaccine, other strains of the virus will take their place.”

The thing is, to reduce the rising cervical cancer mortality rates in Africa, widespread HPV screening and treatment programs are needed now.