Journal List > Korean J Lab Med > v.28(1) > 1011516

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

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.

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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.
kjlm-28-70f1.tif
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.
kjlm-28-70f2.tif
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)
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)
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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