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Outcomes for girls without HPV vaccination in Japan
Comment
Outcomes for girls without HPV vaccination in Japan In Japan, HPV vaccinations became available to girls aged 13–16 years with public aid from 2010 and subsequently became routine for those aged 12–16 years from April, 2013. However, in the spring late spring of 2013, the media repeatedly reported adverse events which were attributed to the HPV vaccination (including pain and motor disability) even though it is not exactly known whether these effects were actually caused by the vaccine. The Japanese Ministry of Health, Labour, and Welfare suspended its active recommendation for girls to receive HPV vaccinations in June, 2013.1–3 As a result, for the fiscal year of 2013, the newly vaccinated rate decreased from the routine rate of approximately 70% per year to 1·1% in girls aged 12 years (Ueda Y, unpublished) and to 3·9% in girls aged 13 years.4 In response to this decision, the International Federation of Gynecology and Obstetrics (FIGO) Gynecologic Oncology Committee and the FIGO subcommittee for Cervical Cancer Prevention released a statement in August, 2013, supporting the safety of HPV vaccination, and the necessity for its continued A
administration in appropriate populations.5 After the FIGO statements, on Aug 29, 2015, the Japan Society of Obstetrics and Gynecology released a statement about the Government’s suspension of recommendation for the use of the HPV vaccine, noting that the current situation in Japan should be evaluated based on scientific evidence.6 However, on Sept 17, 2015, the Ministry of Health, Labour, and Welfare of Japan declared they would not reinstate their previous recommendation for HPV vaccines.7 WHO’s Global Advisory Committee on Vaccine Safety, concerned about the decision following public concerns about adverse effects, stated that “policy decisions based on weak evidence, leading to lack of use of safe and effective vaccines, can result in real harm”.8 Despite these statements from expert committees, encouragement for HPV vaccination by the Japanese Government has not yet been resumed. Furthermore, concerns about this so-called HPV crisis on anti-HPV vaccination has spread from Japan and is now worldwide.9 If the current situation continues in Japan, there is concern that disparities might occur in the incidence of HPV infections, and result in future highly B
Risk of HPV 16/18 infection at 20 years old
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Vaccination restarted in 2020 Vaccination restarted in 2016
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19 93 19 94 19 95 19 96 19 97 19 98 19 99 20 00 20 01 20 02 20 03 20 04 20 05 20 06 20 07 20 08
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Birth year
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Figure: Risk of HPV 16/18 infection at 20 years old (A) Risk of infection when HPV vaccination is given only to girls aged 12–16 years when resuming vaccination encouragement. (B) Risk of infection when HPV vaccination is given to girls aged 12–16 years during the encouragement suspension period in addition to girls aged 12–16 years at the time of the encouragement resumption. Data assumed the risk of HPV 16/18 infection at 20 years old in women having sexual intercourse, who were born in 1993 is 1. Data were based on the proportion of girls having sexual intercourse (we assumed the rate of having sexual intercourse of 65% at 20 years, 55% at 19 years, 42% at 18 years, 25% at 17 years, 15% at 16 years, 5% at 15 years, 2% at 14 years, 1% at 13 years, and 0% at 12 years). Girls were vaccinated at the youngest age during the encouragement period (except in 2013). We assumed that the cumulative rate of vaccination in 2013 in girls aged 12 years was 1% (Ueda Y, unpublished) and in those aged 13 years was 4%,4 the cumulative vaccinated rate after resuming vaccination encouragement in girls is 70%, and that the relationship between the vaccination rate and experience of sexual intercourse is independent.
868
www.thelancet.com/oncology Vol 17 July 2016
Comment
preventable cervical and other HPV-related cancers, depending on an unfortunate year of birth. Based on this scenario, we herein make predictions about infection rate for HPV 16/18 in Japanese women at the age of 20 years, depending on their year of birth. Suppose that vaccination encouragement rapidly resumes in fiscal year 2016 for those aged 12–16 years, the HPV 16/18 infection rate at the age of 20 years for women born in 2000–03 will only slightly increase compared with those born in other years (figure A). More realistically, however, the probability of HPV recommendation resumption this year is extremely low, and it is predicted that a high-infection rate group will be generated for every 1-year delay in resuming this recommendation. For example, according to figure A, in the event that encouragement is not resumed until 2020, girls born between 2000 and 2003 will have a noticeably high HPV 16/18 positive rate compared with female children born in other years. Moreover, even including girls aged 12–16 during encouragement suspension in addition to girls aged 12–16 at the time of vaccination encouragement resumption as a tentative relief measure, if recommendation is not resumed until 2020, some girls might have had sexual intercourse by that time, increasing the HPV infection rate compared with that when resuming vaccination encouragement in 2016 (figure B). By resuming vaccination encouragement in 2016, the number of HPV infections in girls who did not receive HPV vaccines can thus be kept to a minimum. In other words, this year is the last chance to minimise the potential risk of HPV infection for Japanese girls. Should vaccination encouragement resume in a couple of years, girls aged 12–16 years during the encouragement suspension period should at least be included as vaccination participants.
Sadly, Japan’s failure to provide HPV vaccination for young women has now become a global concern. Similar trends are occurring in countries outside of Japan,9 which will lead to increased incidences of HPV-related cancers. Although further efforts are required to overcome the many barriers leading to decreasing cervical cancer mortality, many challenges remain.9 Yusuke Tanaka, *Yutaka Ueda, Tomomi Egawa-Takata, Asami Yagi, Kiyoshi Yoshino, Tadashi Kimura Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan [email protected] YU and TK received lecture fees from GlaxoSmithKline/Japan Vaccine. YU received a lecture fee, research fund (grant number J550703673), and a consultation fee from Merck Sharp & Dohme, and research funding from Japan Agency for Medical Research and Development (grant number 15ck0106103h0102). YT, TE-T, AY, and KY declare no competing interests. 1
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Morimoto A, Ueda Y, Egawa-Takata T, et al. Effect on HPV vaccination in Japan resulting from news report of adverse events and suspension of governmental recommendation for HPV vaccination. Int J Clin Oncol 2015; 20: 549–55. Hanley SJ, Yoshioka E, Ito Y, Kishi R. HPV vaccination crisis in Japan. Lancet 2015; 385: 2571. Gilmour S, Kanda M, Kusumi E, Tanimoto T, Kami M, Shibuya K. HPV vaccination programme in Japan. Lancet 2013; 382: 768. Ueda Y, Enomoto T, Sekine M, Egawa-Takata T, Morimoto A, Kimura T. Japan’s failure to vaccinate girls against human papillomavirus. Am J Obstet Gynecol 2015; 212: 405–06. The International Federation of Gynecology and Obstetrics. FIGO statement on HPV vaccination safety. http://www.figo.org/news/figostatement-hpv-vaccination-safety-0014668 (accessed Feb 1, 2016). Fujii T. Declaration to demand the resumption of recommendations for human papillomavirus (HPV) vaccination for cervical cancer prevention. J Obstet Gynaecol Res 2015; 41: 1859–60. The Ministry of Health, Labour, and Welfare. http://www.mhlw.go.jp/stf/ shingi2/0000102584.html (accessed Feb 1, 2016). WHO. Global Advisory Committee on vaccine safety statement on safety of HPV vaccines. Dec 17, 2015. http://www.who.int/vaccine_safety/ committee/GACVS_HPV_statement_17Dec2015.pdf (accessed Feb 1, 2016). Larson HJ, Wilson R, Hanley S, Parys A, Paterson P. Tracking the global spread of vaccine sentiments: the global response to Japan’s suspension of its HPV vaccine recommendation. Hum Vaccin Immunother 2014; 10: 2543–50.
Phosphenes in patients receiving radiotherapy Phosphenes, named from the ancient Greek phos (light) and phaìnomai (to show), are anomalous visual perceptions of light occurring independently of physiological photonic stimulation of the retina. They can be an early symptom in various diseases of the retina, visual pathways, or CNS, but phosphenes can www.thelancet.com/oncology Vol 17 July 2016
also be experienced by healthy individuals in association with emotional factors, recreational drugs, alcohol, stress, fever, or psychiatric conditions. In oncology, phosphenes are also called light flashes and can occur in the absence of ambient light during radiotherapy for patients with tumours of the CNS, eye, head, and neck. 869
Outcomes for girls without HPV vaccination in Japan In Japan, HPV vaccinations became available to girls aged 13–16 years with public aid from 2010 and subsequently became routine for those aged 12–16 years from April, 2013. However, in the spring late spring of 2013, the media repeatedly reported adverse events which were attributed to the HPV vaccination (including pain and motor disability) even though it is not exactly known whether these effects were actually caused by the vaccine. The Japanese Ministry of Health, Labour, and Welfare suspended its active recommendation for girls to receive HPV vaccinations in June, 2013.1–3 As a result, for the fiscal year of 2013, the newly vaccinated rate decreased from the routine rate of approximately 70% per year to 1·1% in girls aged 12 years (Ueda Y, unpublished) and to 3·9% in girls aged 13 years.4 In response to this decision, the International Federation of Gynecology and Obstetrics (FIGO) Gynecologic Oncology Committee and the FIGO subcommittee for Cervical Cancer Prevention released a statement in August, 2013, supporting the safety of HPV vaccination, and the necessity for its continued A
administration in appropriate populations.5 After the FIGO statements, on Aug 29, 2015, the Japan Society of Obstetrics and Gynecology released a statement about the Government’s suspension of recommendation for the use of the HPV vaccine, noting that the current situation in Japan should be evaluated based on scientific evidence.6 However, on Sept 17, 2015, the Ministry of Health, Labour, and Welfare of Japan declared they would not reinstate their previous recommendation for HPV vaccines.7 WHO’s Global Advisory Committee on Vaccine Safety, concerned about the decision following public concerns about adverse effects, stated that “policy decisions based on weak evidence, leading to lack of use of safe and effective vaccines, can result in real harm”.8 Despite these statements from expert committees, encouragement for HPV vaccination by the Japanese Government has not yet been resumed. Furthermore, concerns about this so-called HPV crisis on anti-HPV vaccination has spread from Japan and is now worldwide.9 If the current situation continues in Japan, there is concern that disparities might occur in the incidence of HPV infections, and result in future highly B
Risk of HPV 16/18 infection at 20 years old
1·0
Vaccination restarted in 2020 Vaccination restarted in 2016
0·8
0·6
0·4
0·2
19 93 19 94 19 95 19 96 19 97 19 98 19 99 20 00 20 01 20 02 20 03 20 04 20 05 20 06 20 07 20 08
19 93 19 94 19 95 19 96 19 97 19 98 19 99 20 00 20 01 20 02 20 03 20 04 20 05 20 06 20 07 20 08
0·0
Birth year
Birth year
Figure: Risk of HPV 16/18 infection at 20 years old (A) Risk of infection when HPV vaccination is given only to girls aged 12–16 years when resuming vaccination encouragement. (B) Risk of infection when HPV vaccination is given to girls aged 12–16 years during the encouragement suspension period in addition to girls aged 12–16 years at the time of the encouragement resumption. Data assumed the risk of HPV 16/18 infection at 20 years old in women having sexual intercourse, who were born in 1993 is 1. Data were based on the proportion of girls having sexual intercourse (we assumed the rate of having sexual intercourse of 65% at 20 years, 55% at 19 years, 42% at 18 years, 25% at 17 years, 15% at 16 years, 5% at 15 years, 2% at 14 years, 1% at 13 years, and 0% at 12 years). Girls were vaccinated at the youngest age during the encouragement period (except in 2013). We assumed that the cumulative rate of vaccination in 2013 in girls aged 12 years was 1% (Ueda Y, unpublished) and in those aged 13 years was 4%,4 the cumulative vaccinated rate after resuming vaccination encouragement in girls is 70%, and that the relationship between the vaccination rate and experience of sexual intercourse is independent.
868
www.thelancet.com/oncology Vol 17 July 2016
Comment
preventable cervical and other HPV-related cancers, depending on an unfortunate year of birth. Based on this scenario, we herein make predictions about infection rate for HPV 16/18 in Japanese women at the age of 20 years, depending on their year of birth. Suppose that vaccination encouragement rapidly resumes in fiscal year 2016 for those aged 12–16 years, the HPV 16/18 infection rate at the age of 20 years for women born in 2000–03 will only slightly increase compared with those born in other years (figure A). More realistically, however, the probability of HPV recommendation resumption this year is extremely low, and it is predicted that a high-infection rate group will be generated for every 1-year delay in resuming this recommendation. For example, according to figure A, in the event that encouragement is not resumed until 2020, girls born between 2000 and 2003 will have a noticeably high HPV 16/18 positive rate compared with female children born in other years. Moreover, even including girls aged 12–16 during encouragement suspension in addition to girls aged 12–16 at the time of vaccination encouragement resumption as a tentative relief measure, if recommendation is not resumed until 2020, some girls might have had sexual intercourse by that time, increasing the HPV infection rate compared with that when resuming vaccination encouragement in 2016 (figure B). By resuming vaccination encouragement in 2016, the number of HPV infections in girls who did not receive HPV vaccines can thus be kept to a minimum. In other words, this year is the last chance to minimise the potential risk of HPV infection for Japanese girls. Should vaccination encouragement resume in a couple of years, girls aged 12–16 years during the encouragement suspension period should at least be included as vaccination participants.
Sadly, Japan’s failure to provide HPV vaccination for young women has now become a global concern. Similar trends are occurring in countries outside of Japan,9 which will lead to increased incidences of HPV-related cancers. Although further efforts are required to overcome the many barriers leading to decreasing cervical cancer mortality, many challenges remain.9 Yusuke Tanaka, *Yutaka Ueda, Tomomi Egawa-Takata, Asami Yagi, Kiyoshi Yoshino, Tadashi Kimura Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan [email protected] YU and TK received lecture fees from GlaxoSmithKline/Japan Vaccine. YU received a lecture fee, research fund (grant number J550703673), and a consultation fee from Merck Sharp & Dohme, and research funding from Japan Agency for Medical Research and Development (grant number 15ck0106103h0102). YT, TE-T, AY, and KY declare no competing interests. 1
2 3 4
5
6
7 8
9
Morimoto A, Ueda Y, Egawa-Takata T, et al. Effect on HPV vaccination in Japan resulting from news report of adverse events and suspension of governmental recommendation for HPV vaccination. Int J Clin Oncol 2015; 20: 549–55. Hanley SJ, Yoshioka E, Ito Y, Kishi R. HPV vaccination crisis in Japan. Lancet 2015; 385: 2571. Gilmour S, Kanda M, Kusumi E, Tanimoto T, Kami M, Shibuya K. HPV vaccination programme in Japan. Lancet 2013; 382: 768. Ueda Y, Enomoto T, Sekine M, Egawa-Takata T, Morimoto A, Kimura T. Japan’s failure to vaccinate girls against human papillomavirus. Am J Obstet Gynecol 2015; 212: 405–06. The International Federation of Gynecology and Obstetrics. FIGO statement on HPV vaccination safety. http://www.figo.org/news/figostatement-hpv-vaccination-safety-0014668 (accessed Feb 1, 2016). Fujii T. Declaration to demand the resumption of recommendations for human papillomavirus (HPV) vaccination for cervical cancer prevention. J Obstet Gynaecol Res 2015; 41: 1859–60. The Ministry of Health, Labour, and Welfare. http://www.mhlw.go.jp/stf/ shingi2/0000102584.html (accessed Feb 1, 2016). WHO. Global Advisory Committee on vaccine safety statement on safety of HPV vaccines. Dec 17, 2015. http://www.who.int/vaccine_safety/ committee/GACVS_HPV_statement_17Dec2015.pdf (accessed Feb 1, 2016). Larson HJ, Wilson R, Hanley S, Parys A, Paterson P. Tracking the global spread of vaccine sentiments: the global response to Japan’s suspension of its HPV vaccine recommendation. Hum Vaccin Immunother 2014; 10: 2543–50.
Phosphenes in patients receiving radiotherapy Phosphenes, named from the ancient Greek phos (light) and phaìnomai (to show), are anomalous visual perceptions of light occurring independently of physiological photonic stimulation of the retina. They can be an early symptom in various diseases of the retina, visual pathways, or CNS, but phosphenes can www.thelancet.com/oncology Vol 17 July 2016
also be experienced by healthy individuals in association with emotional factors, recreational drugs, alcohol, stress, fever, or psychiatric conditions. In oncology, phosphenes are also called light flashes and can occur in the absence of ambient light during radiotherapy for patients with tumours of the CNS, eye, head, and neck. 869