We provide English translations for the convenience of non-Japanese speakers. However, theJapanese shall always prevail over the English in case of any inconsistency.

January 18th, 2023
Dr. Tatsuo Ushiki, President of Niigata University
Dr. Masayuki Sekine, Associate Professor of Department of Obstetrics and Gynecology,
Niigata University Graduate School of Medical and Dental Sciences Graduate School of
Medical and Dental Sciences
Compliance Hotline of Misconduct in Research, Audit Office of Niigata University

Request for Correction to Misidentification in Niigata
University’s public relations article on the "Large epidemiologic
study to evaluate the efficacy and safety of HPV vaccination
against cervical cancer in Japan" (NIIGATA Study) andVerification of the Cause of the Misidentification
Toshihiro Suzuki, Managing Director
YAKUGAI Ombudsperson "Medwatcher Japan"
1-14-4 AM building, Shinjuku, Shinjuku-ku, Tokyo, 160-0022, Japan
yakugai@t3.rim.or.jp
URL: http://www.yakugai.gr.jp/en/

Purpose of the Request
On September 12, 2022, Niigata University School of Medicine and Graduate Schoolof Medical and Dental Sciences published a public relations article on their website titled"Demonstration of Preventive Effect of HPV Vaccine against cervical precancer NIIGATA study: Higher preventive effect with vaccination prior to sexual debut" 1(hereinafter referred to as "the article"). The article misleads its readers about theeffectiveness of the HPV vaccine by misrepresenting the contents of the paper"Effectiveness of human papillomavirus vaccine against cervical precancer in Japan:
Multivariate analyses adjusted for sexual activity" (hereinafter referred to as "the paper").
It was written by Research Associate Risa Kudo, Specially Appointed Professor Takayuki
Enomoto and Associate Professor Masayuki Sekine of the Department of Obstetrics and1

Gynecology, Niigata University Graduate School of Medical and Dental Sciences et al.2.
Therefore, we request the following from Niigata University:
1 Promptly edit the article and correctly explain on its website that according to thepaper, an appropriate comparison of HPV vaccinated and unvaccinated groups failed toconfirm the effectiveness of the HPV vaccine in preventing cervical precancer.
2 Promptly conduct a detailed investigation into why the article contained such
unscientific and unfair content by interviewing its authors and checking for their conflictsof interest, and disclose the results of the investigation.

Reasons for the Request
1 Associate Professor Masayuki Sekine is the contact person for enquiries regarding
this article. The beginning of the article is shown in Figure 1 below.

Figure 1: Extracts from the beginning of the article (Emphasis added by Medwatcher Japan)

Here, the paper is introduced as showing that cervical precancers (high-grade
squamous intraepithelial lesion (HSIL) or worse (HSIL+)) were significantly reduced in
the vaccinated population (vaccine effectiveness rate 64%). Then, the results aredescribed as "the first study in Japan to demonstrate the effectiveness of HPV vaccination
against cervical cytological abnormalities, adjusted for sexual activity including age atsexual debut and number of previous sexual partners."
The article also explains in the “Key Points of the Study Results” section that"significant preventive effectiveness against cervical precancer (high-grade squamous2

intraepithelial lesion: HSIL or worse) was observed in vaccinated women aged 20 to 26years."
2 However, the paper reports that the comparison of the HPV vaccinated and nonvaccinated groups, adjusted for age and sexual activity, showed no statistically significant
difference in the incidence of high-grade squamous intraepithelial lesion or worse(HSIL+), as shown in Figure 2 below. Therefore, the paper straightforwardly introduces
its conclusion in its abstract: "However, analyses of all vaccinated women did not show
significant effectiveness against cytological abnormalities.” The main body of the paper
also explains it as “In terms of effectiveness against HSIL+, VE was 64.0% (95% CI
19.4−83.9%; P = 0.013) in the univariate analysis, 54.1% (95% CI −21.0−82.6%; P =0.116) in Model 1, and 41.1% (95% CI -53.0−77.3%; P = 0.276) in Model 2, with themultivariate analyses adjusted for age and number of sexual partners not showing
significance."
Thus, the paper’s results show no statistically significant difference in the incidence ofHSIL+ in the vaccinated and unvaccinated groups. However, the article places special
emphasis on the effectiveness of the HPV vaccine without mentioning these conclusions.
This is an unscientific and unfair way of introducing a paper.

Figure 2: Table 3 in the paper. Model 1 shows the results of the vaccinated and unvaccinated groups,adjusted for age. No statistically significant difference in the incidence of HSIL+ was shown, as the95% confidence interval crosses 1 and the p-value exceeds 0.05. Model 2 shows the results adjustedfor sexual activity (number of previous sexual partners) in addition to age, and similarly no statisticallysignificant difference was shown for the incidence of HSIL+.

3

To begin with, as is clear from Figure 2 above, the "vaccine effectiveness rate of 64%"
cited by the article is merely a crude analysis that wasn't adjusted for differences between
the two groups, and does not represent the conclusion of the paper.
Therefore, introducing the paper’s conclusion in the article as if it has demonstrated asignificant reduction in cervical precancerous lesions (highly squamous intraepithelial
lesions (HSIL) or worse) in the HPV vaccinated group adjusted for age and sexual activity
is completely false and leads to an apparent misconception about the effectiveness of theHPV vaccine.
Rather, the paper shows that having examined the government's project results ofactively promoting HPV vaccination among young women nationwide, including thosein Niigata Prefecture, they could not confirm the preventive effect of HPV vaccination
against precancerous lesions of cervical cancer between the HPV vaccinated andunvaccinated groups. The paper should be viewed as one of the extremely important
findings that will compel the government to reconsider its active recommendation for
HPV vaccination.
3 To date, the article has been uncritically quoted in various media as having
demonstrated the effectiveness of the HPV vaccine, as exemplified in Figures 3 and 4 at
the end of this document. False information about the HPV vaccine has already been
spread across society due to Niigata university's erroneous public relations activities.
The university should promptly edit the article and correctly explain on its website that
according to the paper, an appropriate comparison of HPV vaccinated and unvaccinatedgroups failed to confirm the effectiveness of the HPV vaccine in preventing precancerous
cervical lesions.
It should also promptly conduct a detailed investigation into why the article containedsuch unscientific and unfair content by interviewing its authors and checking for theirconflicts of interest, and disclose the results of the investigation.
4 Therefore, we would appreciate your reply in writing within one month of receipt of
this document regarding the university's response to this matter.

4

Figure 3: September 14, 2022, Jiji Press website article3

5

Figure 4: October 3, 2022, Japan Medical & Health Informatics Laboratory website article4

1

https://www.med.niigata-u.ac.jp/contents/info/news_topics/209_index.html (Accessed on December 10,2022)
2
Kudo R, Sekine M, Yamaguchi M, Hara M, Hanley SJB, Kurosawa M, Adachi S, Ueda Y, Miyagi E,Ikeda S, Yagi A, Enomoto T. Effectiveness of human papillomavirus vaccine against cervical precancer
in Japan: Multivariate analyses adjusted for sexual activity. Cancer Sci. 2022 Sep;113(9):3211-3220. doi:
10.1111/cas.15471. Epub 2022 Jul 11. PMID: 35730321; PMCID: PMC9459348.
3
https://medical.jiji.com/news/54203 (Accessed on December 10, 2022)
4
https://tokuteikenshin-hokensidou.jp/news/2022/011575.php (Accessed on December 10, 2022)

6