by Zosia Chustecka for Medscape
Updated: 3 September 2015
Japan has put in place a scheme to manage symptoms, especially generalized chronic pain, that have arisen after human papillomavirus (HPV) vaccination given to adolescents to protect against cervical cancer.
Although there have been assurances on the safety of HPV vaccination from many official medical bodies since the vaccines were first introduced — Gardasil (Merck & Co.) in 2006 and Cervarix (GlaxoSmithKline) in 2009 — there have also been persistent reports of rare cases of adverse events. These include case reports in the medical literature of complex regional pain syndrome and postural orthostatic tachycardia syndrome, as previously reported by Medscape Medical News.
In July 2015, the European Medicines Agency announced that it was conducting a safety review of HPV vaccines, which was requested by Denmark, where reports of adverse events after HPV vaccination have been widely reported in the media.
Japan withdrew its recommendation for HPV vaccine in 2013, and has not reversed that decision because of concerns from the public about adverse events, which included long-term pain and numbness, as previously reported by Medscape Medical News.
Since then, various symptoms, especially generalized chronic pain after injection, have been reported.
Last month, guidelines for the evaluation and management of symptoms that begin after HPV vaccine injection were issued to healthcare professionals. The guidelines were edited and approved by the Japan Medical Association (JMA) and the Japanese Association of Medical Sciences (JAMS).
In addition, the Japanese Ministry of Health, Labor, and Welfare has issued a list of medical institutions where people can visit when they have symptoms after HPV injection; there is at least one in each prefecture.
Healthcare workers at those selected institutions are educated by the JMA. However, this does not mean other institutions cannot accept those people with symptoms. The ministry has also issued information regarding HPV vaccine-related health problems and questions, with a telephone helpline.
Guidance for Healthcare Providers
The Japanese guideline was issued in August, and the document was translated for Medscape Medical News by Takeo Fujii, MD, MPH, from the University of Texas M.D. Anderson Cancer Center in Houston.
The guideline recommends that the healthcare provider needs to take a full history and conduct a physical examination. "It is important to ask about all the symptoms with details, including the quality of pain, location of the pain, the severity of the pain, fatigue, motor dysfunction, memory, and recognition. At the same time, taking care of their mental health is also important."
The pain should be considered as three major categories: nociceptive pain (pain caused by direct damage or inflammation to the area), neuropathic pain (peripheral nerve damage from injection or other nervous system diseases), and psychological pain.
When the individual is able to tolerate it, a full neurologic examination is also recommended, and also blood and urine tests are recommended based on the history and physical examination. Referral to a specialist should be considered (e.g., skin discoloration should be referred to a dermatologist).
"Diagnosis should be done based on a comprehensive consideration of history, physical examinations, test results, opinions from specialists, and psychological mood," the guideline says, but also reassures healthcare providers that that they are not "forced to make some definite diagnosis." When the causes of the symptoms are unclear, the recommendation is to tell the individual that there is a possibility that the symptoms might be related to HPV vaccination, although the frequency is very low.
Treatment of the symptoms includes use of oral pain medications, with nonsteroidal anti-inflammatory drugs and acetaminophen recommended for pain, but the guideline also says that the healthcare provider should not hesitate to use narcotics when conservative management does not work.
In addition, substantial sleep management is also important. Exercise and rehabilitation should be recommended. Rehabilitation for pain management is not scientifically proved, the guideline notes. However, regular exercise and especially rehabilitation for the organic joint and muscle dysfunction should be recommended.
The guideline strongly recommends that affected individuals are referred to other facilities, such as specialized medical institutions, rehabilitation facilities, and emergency centers.
It also emphasizes collaboration with local government and schools, and recommends that healthcare providers update their information to schools based upon discussion with people who have symptoms. Such individuals may need absence from class because of their condition.
"We cannot emphasize enough the importance of mental and physical care for the family," the guideline states.
Still Not Recommended in Japan
The new guideline was discussed at a press briefing on August 19, according to a report in Pharma Japan.
The guidelines warn that such symptoms "are easily misinterpreted as malingering or arbitrary," and they caution against using the word "psychogenic" when making differential diagnoses of pain after vaccination, according to the report. "It is difficult to describe pain following inoculation with HPV vaccines as anything other than a syndrome characterized by pain of unknown etiology," the guideline explains.
At the press briefing, Yoshitake Yokokura, president of the JMA, said the government should "wait a little longer" before considering whether to resume actively recommending the use of HPV vaccines, according to the Pharma Japan report.
"Whether active vaccination should be resumed or not will depend on the Ministry of Health, Labor and Welfare," said Fumimaro Takaku, president of JAMS. Noting the vaccines have been available only for a short time, Dr Takaku said: "There's no definitive proof that HPV vaccines can really prevent cervical cancer, but there certainly have been reports in the literature overseas that the incidence of precancerous conditions has declined."
"If it becomes clear that these vaccines prevent the onset of cervical cancer, the government may start actively recommending them again," Dr Yokokura added.