Integration of human papillomavirus type-16 and type-18 is a very early event in cervical carcinogenesis.
OBJECTIVE
Human papillomavirus (HPV) integration is a critical event in cervical carcinogenesis. The aim of this study was to explore the physical status of HPV-16 and HPV-18 during the progression of cervical precancerous lesions.


METHODS
A series of 101 HPV-16 or HPV-18 positive cervical neoplasms (32 cervical intraepithelial neoplasia (CIN) cases and 69 cervical carcinoma (CC) cases) were evaluated. The physical status of both types of HPV was assessed from paraffin-embedded formaldehyde-fixed surgical specimens by real-time PCR.


RESULTS
For HPV-16, integrated DNA was observed in 5 (83.3%) of 6 CIN I cases, 10 (90.9%) of 11 CIN II/III cases, 29 (82.9%) of 35 FIGO (International Federation of Gynecology and Obstetrics) stage I CC cases and 16 (94.1%) of 17 FIGO stages II approximately IV CC cases. For HPV-18, integrated DNA was observed in 3 (50%) of 6 CIN I cases, 5 (55.6%) of 9 CIN II/III cases, 9 (64.3%) of 14 FIGO stage I CC cases, and 1 (33.3%) of 3 FIGO stages II approximately IV CC cases. The mixed form of HPV DNA was the most prevalent physical state in HPV-16. There was no significant difference between the physical state of HPV-16 and HPV-18 DNA with regard to the various grades of cervical lesions.


CONCLUSIONS
These data imply that integration of HPV-16 and HPV-18 DNA into the host genome occurs in the very early stage of cervical neoplastic progression. These early events may play an initiating role in the malignant transformation of HPV-16- and HPV-18-related low-grade lesions into high-grade dysplasia and invasive carcinoma.
Huang
L-W
LW
Department of Obstetrics and Gynecology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan. m002057@ms.skh.org.tw
Chao
S-L
SL
Lee
B-H
BH
D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification / Q000502:physiology*; D052161:Human papillomavirus 18 / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D009367:Neoplasm Staging; D030361:Papillomavirus Infections / Q000150:complications / Q000821:virology; D011230:Precancerous Conditions / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D016662:Virus Integration; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000821:virology*
D004279:DNA, Viral