Correlation of cervical carcinoma and precancerous lesions with human papillomavirus (HPV) genotypes detected with the HPV DNA chip microarray method

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Abstract
BACKGROUND: Human papillomavirus (HPV) infection is considered to play an important role in the development of cervical carcinoma, and it is known that certain HPV types, such as HPV‐16 and HPV‐18, are highly associated with cervical carcinoma. However, the pathologic behavior of other HPV types remains unclear. Recently, a new HPV detection technique, the HPV DNA chip, was introduced. The HPV DNA chip harbors 22 HPV probes and has the advantage of being able to detect 22 HPV types simultaneously. To evaluate the quality of the HPV DNA chip method and to identify HPV types related to cervical carcinoma and precancerous lesions, the authors performed HPV typing in cervical specimens from 1983 patients and compared their cytologic and histologic diagnoses.METHODS: The HPV DNA chip was used for HPV typing. Among 1983 patients who were tested for HPV types, cervical smear cytology was performed in 1650 patients, and 677 of those patients underwent cervical biopsy.RESULTS: Among the 1650 smears that were examined cytologically, 92.7% (114 of 123 smears) of low‐grade squamous intraepithelial lesions (LSILs), 98.1% (106 of 108 smears) of high‐grade squamous intraepithelial lesions (HSILs), and 96.3% (51 of 53 smears) of carcinomas were HPV positive, compared with only 35.1% of smears with normal cytology that were HPV positive. HPV‐16 was the most prevalent type (chi‐square test; P < 0.01) in LSILs (28.5%), in HSILs (51.9%), and in carcinomas (62.5%) followed by HPV‐58 and a group of low‐risk types (HPV‐6, HPV‐11, HPV‐34, HPV‐40, HPV‐42, HPV‐43,and HPV‐44) in LSILs. HPV‐58 (15.7%), HPV‐18 (6.7%), and HPV‐52 (4.6%) were the next most prevalent types after HPV‐16 in HSILs. HPV‐18 (11.4%) and HPV‐58 (11.4%) were the second most common types in carcinomas. HPV‐58 had the highest positive predictive value (54.9%) for the detection of histologically confirmed HSIL or carcinoma, whereas HPV 16 had the highest negative predictive value (80.6%). The sensitivity (96.0%) of the HPV test using the DNA chip method for detecting HSIL or carcinoma was superior compared with the sensitivity of cytologic diagnosis (83.6%).CONCLUSIONS: The HPV DNA chip provides a very sensitive method for detecting 22 HPV genotypes with reasonable sensitivity (96.0%) and reasonable negative predictive value (96.9%), and it overcomes the low sensitivity of cytologic screening for the detection of HSIL or carcinoma. HPV‐58, HPV‐52, and HPV‐56, as well as HPV‐16 and HPV‐18, were associated highly with HSIL and carcinoma in the current large series. In addition, multiple HPV infection was associated less frequently with cervical carcinoma and with precancerous lesions compared with normal cytology. Cancer 2003;97:1672–80. © 2003 American Cancer Society.DOI 10.1002/cncr.11235