Tohoku J. Exp. Med., 2020 June, 251(4)
Human Papillomavirus (HPV) Genotyping Assay Suitable for Monitoring the Impact of the 9-Valent HPV Vaccine
IWAO KUKIMOTO,1 KOJI MATSUMOTO,2 FUMIAKI TAKAHASHI,3 TAKASHI IWATA,4 KOHSEI TANAKA,1,4 MAYUKO YAMAGUCHI-NAKA,1,2 KASUMI YAMAMOTO,5 HIDEAKI YAHATA,6 MAKOTO NAKABAYASHI,7 HISAMORI KATO,8 NAOTAKE TSUDA,9 MAMIKO ONUKI2 and NOBUO YAEGASHI,10 FOR MINT STUDY II GROUP
1Pathogen Genomics Center, National Institute of Infectious Diseases, Tokyo, Japan
2Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan
3Division of Medical Engineering, Department of Information Science, Iwate Medical University, Morioka, Iwate, Japan
4Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan
5Gynecologic Oncology, Hyogo Cancer Center, Akashi, Hyogo, Japan
6Department of Gynecology and Obstetrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan
7Department of Gynecology, Cancer Institute Hospital, Tokyo, Japan
8Department of Gynecology, Kanagawa Cancer Center, Yokohama, Kanagawa, Japan
9Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
10Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
In Japan, a bivalent human papillomavirus (HPV) vaccine against carcinogenic HPV16/18 was licensed in 2009, and a quadrivalent vaccines against HPV16/18 and non-carcinogenic HPV6/11 was licensed in 2011. Recently, the next-generation 9-valent vaccine targeting HPV6/11/16/18/31/33/45/52/58 has been approved. Accurate HPV genotyping is essential for HPV vaccine research and surveillance. The Roche Linear Array (LA) has long been a standard assay for HPV genotyping, but its recent product discontinuation notice has urged us to introduce an alternative assay with comparable performance. In the present study, an in-house HPV genotyping assay that employs PCR with PGMY09/11 primers and reverse blotting hybridization (PGMY-CHUV) was compared with LA to assess genotype-specific agreement. A total of 100 cervical precancer specimens were subjected to both PGMY-CHUV and LA. For detection of genotypes included in the 9-valent vaccine, PGMY-CHUV completely agreed with LA for detection of HPV6, HPV11, HPV16, HPV18, HPV33 and HPV45, and showed near-complete agreement for HPV31 and HPV58 (98% and 99%, respectively). Moreover, PGMY-CHUV detected a significantly higher prevalence of HPV52 than LA (22% vs. 14%, P = 0.008 by McNemar's exact test), with 92.0% overall agreement, 63.6% positive agreement and a kappa value of 0.73. Most (87.5%) of HPV52 discordant cases involved mixed infections with HPV35 or HPV58. In conclusion, while the two assays present equivalent data for assessing the effectiveness of the bivalent and quadrivalent vaccines, PGMY-CHUV is more suitable for evaluating the impact of the current 9-valent vaccine because of its superior detection of HPV52 in co-infection cases.
Keywords —— cervical cancer; cervical intraepithelial neoplasia; genotyping; human papillomavirus; vaccine
© 2020 Tohoku University Medical Press
===============================
Tohoku J. Exp. Med., 2020, 251, 287-294
Correspondence: Koji Matsumoto, Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
e-mail: matsumok@mui.biglobe.ne.jp