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Type‐dependent association between risk of cervical intraepithelial neoplasia and viral load of oncogenic human papillomavirus types other than types 16 and 18
Author(s) -
Fu Xi Long,
Schiffman Mark,
Ke Yang,
Hughes James P.,
Galloway Denise A.,
He Zhonghu,
Hulbert Ayaka,
Winer Rachel L.,
Koutsky Laura A.,
Kiviat Nancy B.
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30594
Subject(s) - medicine , hazard ratio , viral load , squamous intraepithelial lesion , confidence interval , cervical intraepithelial neoplasia , cervical cancer , oncology , gastroenterology , proportional hazards model , cancer , immunology , virus
Studies of the clinical relevance of human papillomavirus (HPV) DNA load have focused mainly on HPV16 and HPV18. Data on other oncogenic types are rare. Study subjects were women enrolled in the atypical squamous cells of undetermined significance (ASC‐US) and low‐grade squamous intraepithelial lesion (LSIL) triage study who had ≥1 of 11 non‐HPV16/18 oncogenic types detected during a 2‐year follow‐up at 6‐month intervals. Viral load measurements were performed on the first type‐specific HPV‐positive specimens. The association of cervical intraepithelial neoplasia grades 2–3 (CIN2/3) with type‐specific HPV DNA load was assessed with discrete‐time Cox regression. Overall, the increase in the cumulative risk of CIN2/3 per 1 unit increase in log 10 ‐transformed viral load was statistically significant for four types within species 9 including HPV31 (adjusted hazard ratio [HR adjusted ] = 1.32: 95% confidence interval [CI], 1.14–1.52), HPV35 (HR adjusted = 1.47; 95% CI, 1.23–1.76), HPV52 (HR adjusted = 1.14; 95% CI, 1.01–1.30) and HPV58 (HR adjusted = 1.49; 95% CI, 1.23–1.82). The association was marginally significant for HPV33 (species 9) and HPV45 (species 7) and was not appreciable for other types. The per 1 log 10 ‐unit increase in viral load of a group of species 9 non‐HPV16 oncogenic types was statistically significantly associated with risk of CIN2/3 for women with a cytologic diagnosis of within normal limits, ASC‐US, or LSIL at the first HPV‐positive visit but not for those with high‐grade SIL. Findings suggest that the viral load‐associated risk of CIN2/3 is type‐dependent, and mainly restricted to the species of HPV types related to HPV16, which shares this association.