Preventable Deaths

By+Li+Li

Cancer kills， but some cancers have become avoidable due to the latest development of vaccines against certain viral infections. Cervical cancer， the third most common cancer in women， is one such preventable cancer.

Virtually all cervical cancer cases are linked to infections caused by the human papillomavirus （HPV）. As early as in the 1990s， research established a consistent association between HPV and cervical cancer. In 2006， the U.S. Food and Drug Administration approved the first preventative HPV vaccine. However， though several HPV vaccines have been approved in more than 140 countries and regions， they are still unavailable on the Chinese mainland， where around 80，000 women died from cervical cancer and 150，000 new cases were diagnosed last year.

Cervical cancer was little known on the Chinese mainland until the untimely death of Hong Kong Cantopop icon Anita Mui Yim Fong at the age of 40 at the hands of the disease in December 2003. Young female mainlanders who want the vaccination， most of them well-educated and well-off， typically go to Hong Kong or Macao， where HPV vaccines are available.

There is no annual figure of women from the Chinese mainland receiving vaccination in Hong Kong， but their increasing popularity can be seen through a number of foolproof guides on the Internet.

Prolonged review

HPV infections are very common， but usually go away on their own. However， persistent HPV infections can cause cellular abnormalities that could develop into cervical cancer if not treated. Two HPV vaccines are currently on the market， Gardasil and Cervarix. Both of them protect against HPV-16 and HPV-18， which are responsible for about 70 percent of cervical cancer cases.

“The two HPV vaccines should be introduced as part of a coordinated strategy to prevent cervical cancer and other HPV-related ailments，” according to the WHOs HPV vaccine position paper published in April 2009. At present， many developed countries have integrated HPV vaccines into their national immunization programs and provide them free of charge to adolescents. Furthermore， HPV vaccines have been licensed in numerous developing countries， such as Mexico and Kenya.

However， vaccines made by two multinational pharmaceutical companies—the UKbased Glaxo Smith Kline Biologicals and the U.S.-based Merck—are still undergoing regulatory review and as a result they have not been approved for use on the Chinese mainland.endprint

According to Chinas regulations on drug registration， which went into effect on October 1， 2007， all overseas producers of vaccines must perform a local clinical trial. Since the original global clinical trials for HPV vaccines recommended by the WHO did not include Chinas mainland， delays in vaccine availability are unavoidable.

Moreover， the regulations require evaluating efficacy of candidate HPV vaccines against moderate to severe cervical precancer， which requires a control group in the trials to be administered a placebo instead of the vaccination. The China Food and Drug Administration （CFDA）， the national drug regulator， insists on approving the vaccines only after enough people among the placebo control group develop cervical cancer or grade II cervical interstitial neoplasia.

However， many countries， such as India and Japan， have followed a suggestion of the WHO in evaluating persistent HPV infections rather than pre-cancerous diseases as a surrogate endpoint as the time between the initial HPV infection and development of cervical cancer is usually decades.

In China， many gynecologists and epidemiologists have called for the regulatory authority to follow suit and expedite the approval process.

Liu Jihong， the chief cervical cancer specialist at Guangzhou-based Sun Yat-sen University Cancer Center in south Chinas Guangdong Province， told newspaper Southern Weekly that her facility treats more than 1，000 cervical cancer patients every year， which is equivalent to the total new cases diagnosed in Australia in the same period. Sometimes， she has to perform three operations on patients with cervical cancer in a single day.

The cancer center Liu works for is one of the four medical facilities participating in the clinical trials of HPV vaccines in China， which started in 2009.

When Lius team submitted the Phase III trial efficacy data on Gardasil to the CFDAs predecessor， then known as the State Food and Drug Administration （SFDA）， in 2012， the agency ruled that too few cases of grade II cervical interstitial neoplasia had rendered the presentation as insufficient. The presentation used a composite index combining persistent HPV infections with grade II cervical interstitial neoplasia. The SFDA required Lius center to extend the trial to gather more data.

Liu admitted that this was a daunting task， even after she and her colleagues increased the frequency of trial participants visits to once every three months.endprint

Two domestic companies are also independently developing HPV vaccines. The candidate vaccine developed by Xiamen Innovax Biotech in southeast Chinas Fujian Province has also entered Phase III trials. An anonymous executive from the company said that if persistent HPV infections are used as a measure， rather than pre-cancerous disease， the companys clinical trials can be shortened by two to three years and the vaccine can be expected to become available in 2018.

Although the vaccine is approved for women up to the age of 26 in most countries， it is generally considered to be best administered between 9 to 15 years old in China， before girls become sexually active and are potentially exposed to HPV.

Without other preventive measures such as screening， a national HPV vaccination program for all 9-15-year-old girls between 2006 and 2012 could have prevented 381，000 cervical cancer cases and 212，000 related deaths in the future when they begin to age. Furthermore， if vaccines are unavailable each additional year will cause 8.43 million girls in this age group to lose their opportunity for vaccination， according to a paper authored by two experts from the Cancer Institute/Hospital， Chinese Academy of Medical Sciences. The paper， titled The Impact of HPV Vaccination Delays in China， was published in the Netherlands-based journal Vaccine in June 2013.

However， some people believe that the prudence exhibited by the Chinese regulatory authority is nothing but necessary.

Liu Peng， an associate professor at the School of Public Administration and Policy of Beijing-based Renmin University of China， told Southern Weekly that the approval of imported drugs has to consider the factors of genetic differences， a domestic populations medication habits and drug risk tolerance as well as trial results from other countries. He said that with Chinas vast population， even a small rate of side effects could affect a large number of people.

Last June， the Japanese Ministry of Health， Labor， and Welfare instructed local governments not to promote the use of HPV vaccines， citing concerns from the public about adverse effects， such as long-lasting pain and numbness.

Guangzhou-based Nanfang Daily on May 13 quoted a joint study on HPV infections conducted by the Chinese Center for Disease Control and Prevention and Peking University First Hospital. The study concluded that HPV 16， HPV 52 and HPV 58 are the most common HPV types found among high-risk groups on the Chinese mainland—a stark difference from developed countries， where HPV 18 is the most common.endprint

But the HPV vaccines being developed by two Chinese companies also target HPV 16 and HPV 18.

Cost effectiveness

Even after the use of HPV vaccines is ratified on the Chinese mainland， the costs could become a major barrier to making them widely used.

According to the U.S. Centers for Disease Control and Prevention， as of July 2012， the retail price for either vaccine is about $130 per dose （$390 for full series）， making it expensive even by the standards in developed countries. According to a survey on the acceptability of HPV vaccination among 2，895 parents of young adolescents across China between November 2011 and May 2012， in respect to vaccine pricing， 71.6 percent were willing to pay 300 yuan （$48） or below， and only 11.8 percent accepted a price of 500 yuan （$81） or above.

In the same survey， only 25.1 percent of the parents had heard of HPV and only 15.6 percent had heard of HPV vaccines. The survey also found that acceptance of HPV vaccination for young adolescents among parents was only 36.2 percent.

With the approval of HPV vaccines around the corner in China， health policy makers will have to weigh up their options for the best ways to prevent cervical cancer. Like other developing countries， China has to decide whether to invest more in vaccination or in screening， which is cheaper and proves effective in reducing the majority of cervical cancer cases.

Researchers said that cervical cancer screening will continue to be needed for the foreseeable future as current vaccines include only certain high-risk HPV types and a large number of women are already infected.

Local governments in China launched free screening programs for breast and cervical cancers for women in 2008. However， participation rates are generally low due to the lack of campaigns advertising the programs.

“Since cervical cancer is the only cancer with a clearly identified cause， we need to eliminate it through vaccination， regular screening and earlier diagnosis，” said Lang Jinghe， head of the Department of Obstetrics and Gynecology at Peking Union Medical College Hospital， at a national seminar on cervical cancer prevention in April.endprint