Jimin Kahng; Hee-Jeong Lee

doi:10.3343/kjlm.2008.28.1.70

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Kahng and Lee: Clinical Efficacy of HPV DNA Chip Test in the Era of HPV Vaccination – 1,211 Cases, A Single Institution Study -

Original Article

Korean J Leg Med 2008;28(1):70-78.

Published online: 14 February 2008

DOI: https://doi.org/10.3343/kjlm.2008.28.1.70

Clinical Efficacy of HPV DNA Chip Test in the Era of HPV Vaccination – 1,211 Cases, A Single Institution Study -

Jimin Kahng, M.D.¹, Hee-Jeong Lee, M.D.²

¹Department of Laboratory Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea

²Department of Hospital Pathology, The Catholic University of Korea College of Medicine, Seoul, Korea

Received 16 November 200717 December 2007 Accepted 20 December 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Human papillomavirus (HPV) prophylactic vaccines, bivalent types for HPV-16/18 with 70% prophylactic expectation, have been developed based on the genotypes found prevalent in the western countries, but little is known for those in Korea. Using a DNA chip test, we evaluated the clinical efficacy of HPV genotype based on cervical abnormalities.

Methods

As the initial diagnostic tests, HPV DNA chip tests and Papanicolaou smear (PAP) were used for 1,211 subjects. Cervical colposcopy directed biopsies were performed for 626 among the 1,211 subjects within one month.

Results

The most frequently found genotypes in all HPV-positive specimens (n=445) were HPV-16 (22.0%), 58 (13.9%), 52 (11.0%), 51 (9.0%), 56 (8.5%), and 18 (7.2%). HPV prevalence was significantly higher in specimens where PAP and biopsy results were closer to malignancy. The HPV genotype distribution of the histologically confirmed cervical high-grade squamous intraepithelial lesions (HSIL) or carcinoma cases showed HPV-16, 58, 52, 18, and 33, in descending order. The HPV DNA chip sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the detection of cervical HSIL or carcinoma were 76.9%, 70.1%, 72.1%, and 75.8%, respectively, Of these, the sensitivity and NPV were higher than those of PAP. PPV and NPV of HPV-16 were 90.5% and 60.7%, respectively, being the highest among the genotypes.

Conclusions

We confirmed that HPV-16 genotype was also very important for the diagnosis of HSIL and cervical carcinoma in Korea. However, contrary to the findings in the western countries, the prevalence of HPV-58 was higher than that of HPV-18. Moreover, as the other HPV genotype reports were rare in Korea, further studies are required with the HPV DNA chip test before the nationwide adoption of the vaccines.

Keywords: Human papillomavirus, Genotypes, DNA chip test, Clinical efficacy

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Fig. 1.

Percent of patients infected with individual human papillomavirus (HPV) genotypes among age groups. Each type included single and multiple infections.

Fig. 2.

Distribution of percent of patients infected with the individual high-risk human papillomavirus (HPV) genotypes. Each type included single and multiple infections. HPV-16 was the most prevalent type in HPV-infected women (chi-square test: P<0.001). LSIL, low-grade squamous intraepithelial lesion.

Table 1.

Prevalence of human papillomavirus (high risk groups) according to the results of Papanicolaou smear and biopsy

PAP	Positive cases/total (%)	Biopsy	Positive cases/total (%)
PAP-normal	84/432 (19.4)	Biopsy-normal	31/106 (29.3)
ASC-US	142/525 (27.0)
PAP-LSIL	108/207 (52.2)	Biopsy-LSIL	164/416 (39.4)
PAP-high risk lesion	35/47 (74.5)	Biopsy-high risk lesion	81/104 (77.9)
Total	369/1,211 (30.5)	Total	276/626/ (44.1)

PAP-high risk lesion includes high-grade squamous intraepithelial lesion, carcinoma in situ (CIS), and invasive carcinoma. Biopsy-LSIL includes koilocytosis and cervical intraepithelial neoplasia 1 (CIN 1). Biopsy-high risk lesion includes CIN 2, CIN 3, CIS, and invasive carcinoma.

Statistically significant figures are in bold.

Abbreviations: PAP, Papanicolaou smear; ASC-US, atypical squamous cell of undetermined significance; LSIL, low-grade squamous intraepithelial lesion.

Table 2.

The distribution of human papillomavirus (HPV) high risk genotypes by HPV DNA chip according to cervical cytology

HPV genotype	N. of patients (% in total cases/% in positive cases)
HPV genotype	Total	PAP-normal	ASC-US	PAP-LSIL	PAP-high risk lesion
16	98	29	31	26	12
		(6.7/34.5)	(5.9/21.8)	(12.6/24.1)	(25.5/34.3)
58	62	21	23	10	8
		(4.9/25.0)	(4.4/16.2)	(4.8/9.3)	(17.0/22.9)
52	49	8	17	20	4
		(1.9/9.5)	(3.3/12.0)	(9.7/18.5)	(8.5/11.4)
51	40	9	14	15	2
		(2.1/10.7)	(2.7/9.9)	(7.2/13.9)	(4.3/5.7)
56	38	7	14	16	1
		(1.6/8.3)	(2.7/9.9)	(7.7/14.8)	(2.1/2.9)
18	32	5	19	4	4
		(1.2/6.0)	(3.6/13.4)	(1.9/3.7)	(8.5/11.4)

PAP-high risk lesion includes high-grade squamous intraepithelial lesion, carcinoma in situ (CIS), and invasive carcinoma.

Statistically significant figures are in bold (P<0.05).

Abbreviations: PAP, Papanicolaou smear; ASC-US, atypical squamous cell of undetermined significance; LSIL, low-grade squamous intraepithelial lesion.

Table 3.

The distribution of human papillomavirus (HPV) high risk genotypes by HPV DNA chip according to cervical histology

HPV genotype	N. of patients (% in total cases/% in positive cases)
HPV genotype	Total	Biopsy-normal	Biopsy-LSIL	Biopsy-high risk lesion
16	73	4 (3.8/12.9)	31 (7.5/18.9)	38 (36.5/46.9)
58	42	6 (5.7/19.4)	21 (5.0/12.8)	15 (14.4/18.5)
52	38	5 (4.7/16.1)	23 (9.7/14.0)	10 (9.6/12.3)
51	30	4 (3.8/12.9)	23 (7.2/14.0)	3 (2.9/3.7)
56	28	1 (0.9/3.2)	24 (7.7/14.6)	3 (2.9/3.7)
18	25	0 (0.0/0.0)	16 (1.9/9.8)	9 (8.7/11.1)

Statistically significant figures are in bold (P<0.05).

Biopsy-LSIL includes koilocytosis and cervical intraepithelial neoplasia 1 (CIN 1). Biopsy-high risk lesion includes CIN 2, CIN 3, CIS, and invasive carcinoma.

Abbreviation: LSIL, low-grade squamous intraepithelial lesion.

Table 4.

Comparison of test performances of Papanicolaou smear and human papillomavirus testing by DNA chip for the detection of histologically confirmed high-grade squamous intraepithelial lesion or the worse cases

	Any HPV	HPV-16	HPV-58	HPV-52	HPV-35	HPV-33	PAP
Sensitivity (%)	76.9	36.5	13.5	9.6	4.8	8.7	53.4
Specificity (%)	70.8	96.2	94.3	95.2	96.2	99.1	69.2
PPV (%)	72.1	90.5	70.0	66.7	55.6	90.0	74.6
NPV (%)	75.8	60.7	52.6	51.8	50.8	52.5	46.8

Abbreviations: HPV, human papillomavirus; PPV, positive predictive value; NPV, negative predictive value.

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