Human papillomavirus genotype study using next-generation sequencing technology = 차세대 시퀀싱 기술을 이용한 인간 유두종 바이러스 유전자형 연구

국문 초록 (Abstract)

인간 파필로마바이러스(HPV)는 자궁경부암과 연관돼 있으며 현재까지 100종 이상이 확인되었다. 이번 연구에서는 2436명의 여성에게서 채취한 샘플을 차세대 염기서열분석(NGS) 기술로 유전자형으로 확인하여 다중 감염, 감염된 바이러스의 유전자형, 임상증상 간의 관계를 밝혀냈다. NGS 결과 중 고위험형에서는 58, 56, 16type의 유전자형이 가장 많았고, 저위험형에서는 90, 54, 81type의 유전자형이 가장 많았다. 단일 유형만 감염된 경우에서는 의미미결정 비정형 편평 세포(ASCUS)나 고등급 편평 상피 변병(HSIL)이 11.45%를 차지했고, 2종 이상의 다중 감염이 된 경우에서는 27.17%를 차지했다. ASCUS 또는 HSIL은 고위험형만 다중 감염된 경우에서 29.79%를 차지했으며, 고위험형과 저위험형이 같이 다중 감염된 경우에서 29.81%를, 저위험형에만 다중 감염에서만 총 18.79%를 차지했다(P ≤ 0.0001). 이는 고위험 HPV와 공동 감염되었을 때 저위험 HPV가 세포 병변을 일으킬 가능성이 더 높았다는 것을 의미한다. 이러한 결과는 세포 병변이 일어나는 빈도는 다중 감염된 HPV의 유전자형과 그 수에 영향을 받는 다는 것을 보여주었다. 이 연구의 결과에서 다중 감염이 ASCUS 이상의 조직에서 많이 관찰되었다. 아마도 이것이 질병의 중요도를 결정하는 지표가 될 수 있으리라 기대된다. NGS를 이용한 HPV의 유전자형 확인은 정확한 다중 감염 감별이 가능함으로 HPV 진단 및 치료에 도움을 줄 수 있다. 앞으로 NGS를 이용하여 다중 감염된 유전자형이 확인된 환자에서의 지속적인 모니터링이나 감염 기전 등을 추가 연구해야 할 것이다.

다국어 초록 (Multilingual Abstract)

Human papillomavirus (HPV) has been identified as having more than 100 different types, some of which are associated with cancer. The most representative example is that cervical cancer is associated with 16 and 18 type. Here, the relationship between multiple infections, virus types, and cytology results was revealed by typing 2436 samples taken from Korean women using next-generation sequencing (NGS). multiple infections NGS found that 58, 56, and 16 types were the most common in high-risk types, while 90, 54, and 81 types were most common in low-risk types. Atypical squamous cells of undetermined significance (ASCUS) or high-grade squamous intraepithelial lesion (HSIL) were 11.45% in single-type cases, whereas they were 27.17% with multiple infections of 2 types. ASCUS or HSIL were 29.79% in only high-risk type multiple infections, and were 29.81% mixed high and low-risk types multiple infections, whereas they were 18.79% in only low-risk -type multiple infections (P ≤ 0.0001). This means that low-risk HPVs, when they were co-infected with high-risk HPVs, were more likely to cause cell lesions. Taken together, these results showed that the higher the multiple infection, the greater the frequency of cell lesions. Thus, to predict the clinical symptoms, it is necessary to confirm the HPV type and multiple infections using NGS.

목차 (Table of Contents)

• Contents
• Ⅰ. Abstract ························································ 1
• Ⅱ. Introduction ···················································· 3
• Ⅲ. Materials and Methods ·········································· 6
• Ⅳ. Results ························································ 11
• Ⅴ. Discussion ···················································· 22
• Ⅵ. References ···················································· 26
• Ⅶ. Acknowledgement ············································· 33
• Ⅷ. 국문 논문제출서 ················································ 35
• Ⅸ. 국문 인준서 ···················································· 36
• Ⅹ. Abstract in Korean ············································ 37