NL

LSILCIN I

HPV

ASCUS

CIN II

HSIL

CIN III

SCC

HPV

병리 검사는 병리과에서 합니다.

• 세포와 조직을 이용한 분자병리검사는 병리과에서 시행되어야!!!

– 진단의 한계를 넘어서는 predictor가치• 반드시 진단과 함께!!!• 반드시 진단과 함께!!!

• 임상의에게 가장 정확하고 신뢰성있는 정보 제공

– Non-Human microbe/virus detection

– Human oncogene as Px factor

– Sensitivity test before targeted therapy• Breast, lung, pancreas, colon, stomach ca

HPV types associated with diseases HPV types associated with diseases

Bosch et al., 1995; Bonnez & Reichman 2000; Burd, 2003

Latent InfectionLatent Infection

• Formal definition: Presence of HPV DNA in the absence of virion production

• Practical definition:

Detectable HPV DNA in the absence of identifiable lesion

-- HPV DNA positive, normal cytology

-- Equated with occult infection

Persistence of HPV80% clearance by host immune systemDefinition: HPV DNA same type is detected on at least two occasions over a period of one or more years. HPV persistence: 20% of HPV infection

Patient age: 30yr>HPV genotypes:high-riskHPV multiplicity:multiple

invasive cancer: 30% of persistence

HPV DNA testHPV DNA test

국내 시장 점유 문제점

�� High prevalence in clinically normal women High prevalence in clinically normal women

�� Most infections are transient Most infections are transient

�� Repeat testing needed in 6Repeat testing needed in 6--12 months to 12 months to

determine HPV persistencedetermine HPV persistence

HC 2 (Digene/Qiazen)

HPV DNA Chipdetermine HPV persistencedetermine HPV persistence

�� High risk HPV does not always lead to the High risk HPV does not always lead to the

SIL.SIL. Diverse range assays - few

standardized, commercially available

�� lowlow risk group ignored? Nothing with HSIL?risk group ignored? Nothing with HSIL?

� Analytical vs clinical sensitivity

� Standard? QA, QC

� International standards: ISO/TC212

HPV DNA Chip

Multiplex PCR(Seegene)

Amplicor (Roche)

PreTect HPV-proofer(Norchip)

Comparison of KFDA approval HPV items

Merit Drawback Huddle

HC2 Low sensitivty-5,000genome

No Type-specificNo multiple types

No LR-HPV

Multiplex PCR High sensitivity-1~10 Semi-specific Reproducibility

DNA Chip-conventional

High sensitivity No quantityLow specificity

Cross-reactionLaborious

DNA Chip-9G High sensitivity Less well known Replacing tool

Performance characteristicsPerformance characteristics

Designation Probes/primersReaction

product

Analytical

sensitivity, fg

detectable

types

Hybrid

ization

HC2 HPV DNA

assay

Mixture of

RNA probes

DNA/RNA

hybrids25–75 13

PCRMY09/11 Dot blot Degenerate primer 450 bp 0.1–100 39

PCR PGMY09/11

reverse LBA

Mixture of

consensus primers450 bp 0.1 27

PCR GP5+/GP6+ EIA

ELISA systemConsensus primers 150 bp 0.5–10 20

PCRGP5+/6+ reverse

LBAConsensus primers 150 bp 0.5–10 37

PCRSPF-PCR

reverse LiPA

Mixture of

consensus primers65 bp 0.1–10 43

IftnerIftner T, et al. J T, et al. J NatlNatl Cancer Inst Cancer Inst MonogrMonogr. 2003;(31):80. 2003;(31):80--8. 8.

The concept of HPV load with clinical behaviorThe concept of HPV load with clinical behavior

SnijdersSnijders P, et al. J P, et al. J PatholPathol 2003; 201: 12003; 201: 1––6.6.

Modified from the Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening.

(Wright TC Jr, et al. Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening. Obstet Gynecol 2004 ; 103 :304 – 9.)

Kahn, JNCI, 2005

비정상비정상자궁경부자궁경부세포검사를세포검사를보인보인환자의환자의처치에처치에있어서있어서 HPV DNA testing HPV DNA testing

�� ASCASC--US/LSIL US/LSIL 환자의환자의처치처치및및추적추적검진검진

–– 고위험군고위험군 HPV DNA testing : HPV DNA testing : 연연 11회회시행시행 급여급여인정인정

�� 조직검사상조직검사상 CIN 1CIN 1으로으로확진된확진된환자의환자의추적추적검진검진

–– 고위험군고위험군 HPV DNA testing : HPV DNA testing : 연연 11회회시행시행 급여급여인정인정

CIN II/III CIN II/III 환자의환자의치료치료전전,,후후검사로서검사로서HPV DNA testing HPV DNA testing

�� 고위험군고위험군 HPV DNA testing: HPV DNA testing:

–– 치료치료전전 11회회시행시행급여급여인정인정

–– 치료치료후후최소최소 66개월개월후후 11회회시행시행급여급여인정인정–– 치료치료후후최소최소 66개월개월후후 11회회시행시행급여급여인정인정

�� 치료치료후후시행한시행한고위험군고위험군 HPV DNA testingHPV DNA testing이이양성양성

–– 66--1212개월개월간격으로간격으로고위험군고위험군 HPV DNA testingHPV DNA testing을을

반복반복시행시행 급여급여인정인정

병리 검사는 병리과에서 합니다.

• 세포와 조직을 이용한 분자병리검사는 병리과에서 시행되어야!!!

– 진단의 한계를 넘어서는 predictor가치• 반드시 진단과 함께!!!• 반드시 진단과 함께!!!

• 임상의에게 가장 정확하고 신뢰성있는 정보 제공

– Non-Human microbe/virus detection

– Human oncogene as Px factor

– Sensitivity test before targeted therapy• Breast, lung, pancreas, colon, stomach ca