TY - JOUR
T1 - Human papillomavirus (Hpv) genotyping assay suitable for monitoring the impact of the 9-valent hpv vaccine
AU - MINT Study II Group
AU - Kukimoto, Iwao
AU - Matsumoto, Koji
AU - Takahashi, Fumiaki
AU - Iwata, Takashi
AU - Tanaka, Kohsei
AU - Yamaguchi-Naka, Mayuko
AU - Yamamoto, Kasumi
AU - Yahata, Hideaki
AU - Nakabayashi, Makoto
AU - Kato, Hisamori
AU - Tsuda, Naotake
AU - Onuki, Mamiko
AU - Yaegashi, Nobuo
N1 - Funding Information:
This work was supported by funding from the Japan Agency for Medical Research and Development (AMED) under grant number JP20fk0108098, and the Ministry of Health, Labor, and Welfare of Japan. The funding organizations played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Publisher Copyright:
© 2020 Tohoku University Medical Press.
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
KW - Cervical cancer
KW - Cervical intraepithelial neoplasia
KW - Genotyping
KW - Human papillomavirus
KW - Vaccine
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U2 - 10.1620/tjem.251.287
DO - 10.1620/tjem.251.287
M3 - Article
C2 - 32759554
AN - SCOPUS:85089171101
SN - 0040-8727
VL - 251
SP - 287
EP - 294
JO - Tohoku Journal of Experimental Medicine
JF - Tohoku Journal of Experimental Medicine
IS - 4
ER -
