title: Distribution and viral load of eight oncogenic types of human papillomavirus (HPV) and HPV 16 integration status in cervical intraepithelial neoplasia and carcinoma.
abstract: Current human papillomavirus (HPV) DNA testing using pooled probes, although sensitive, lacks specificity in predicting the risk of high-grade cervical intraepithelial neoplasia (CIN 2/3) progression. To evaluate selected HPV genotyping, viral load, and viral integration status as potential predictive markers for CIN progression, we performed HPV genotyping in formalin-fixed, paraffin-embedded cervical tissue with cervical carcinoma (29 cases) and CINs (CIN 1, 27 cases; CIN 2, 28 cases; CIN 3, 33 cases). General HPVs were screened using consensus primers GP5+/GP6+ and PGMY09/11. HPV genotyping and viral load measurement were performed using quantitative real-time PCR for eight oncogenic HPV types (16, 18, 31, 33, 35, 45, 52, and 58). HPV 16 viral integration status was evaluated by measuring HPV 16 E2/E6 ratio. We observed that HPV DNA positivity increased in parallel with the severity of CINs and carcinoma, with 59% positivity in CIN 1, 68% in CIN 2, 76% in CIN 3, and 97% in carcinoma (P trend=0.004). The eight oncogenic HPV types were significantly associated with CIN 2/3 (81%) and carcinoma (93%) (odds ratio (OR), 15.0; 95% confidence interval (CI), 5.67-39.76; P<0.0001) compared with the unknown HPV types (OR, 2.87; 95% CI, 0.89-9.22; P=0.08). HPV 16 was the predominant oncogenic HPV type in CIN 2/3 (51%) and carcinoma (71%) and integrated significantly more frequently in carcinoma than in CIN 2/3 (P=0.004). No significant differences in viral load were observed across the disease categories. Our findings suggest that selected genotyping for the eight oncogenic HPV types might be useful in separating women with a higher risk of CIN progression from those with a minimal risk. We also conclude that the HPV 16 integration status has potential to be a marker for risk assessment of CIN progression.
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA. mguo@mdanderson.org
authors.forename: Ming
authors.initials: M
authors.lastname: Guo
authors.forename: Nour
authors.initials: N
authors.lastname: Sneige
authors.forename: Elvio G
authors.initials: EG
authors.lastname: Silva
authors.forename: Yee Jee
authors.initials: YJ
authors.lastname: Jan
authors.forename: David E
authors.initials: DE
authors.lastname: Cogdell
authors.forename: E
authors.initials: E
authors.lastname: Lin
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D030361:Papillomavirus Infections / Q000097:blood / Q000150:complications* / Q000473:pathology; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000473:pathology / Q000821:virology*; D019562:Viral Load; D016662:Virus Integration / Q000235:genetics; D002578:Uterine Cervical Dysplasia / Q000097:blood / Q000473:pathology / Q000821:virology*
chemical_list: D004279:DNA, Viral