Human Papillomavirus L1 Capsid Protein and Human Papillomavirus Type 16 as Prognostic Markers in Cervical Intraepithelial Neoplasia 1

Choi, Young Sam; Kang, Woo Dae; Kim, Seok Mo; Choi, Yoo Duk; Nam, Jong Hee; Park, Chang Soo; Choi, Ho Sun

doi:10.1111/igc.0b013e3181cd184c

Cited by 22 publications

(11 citation statements)

References 19 publications

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“…(22–25) A lower proportion of the positive cases in histology compared to cytology specimens is likely related to the fact that in the majority of lesions the expression of capsid proteins is restricted to the most superficial layers of the epithelium. Thus, the keratinocytes in the superficial layers are most readily detached and harvested during sampling for a Pap test, but might also be inadvertently removed from the epithelial surface during colposcopy (mucous clearing etc.)…”

Section: Discussionmentioning

confidence: 99%

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Immunohistochemical detection of human papillomavirus capsid proteins L1 and L2 in squamous intraepithelial lesions: potential utility in diagnosis and management

et al. 2013

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While cervical cancer screening relies on cervical cytology and high-risk HPV detection, histologic diagnosis, and specifically lesion grade, is the main parameter that drives clinical management of screen-positive women. Morphologically diagnosed squamous intraepithelial lesions (SIL/CIN) regress spontaneously in more than half of the cases, but identifying those likely to persist and progress is not currently possible based upon morphology. Lack of major capsid protein L1 expression has been suggested as a feature in progressive lesions, while expression of the minor capsid protein L2 has not been extensively evaluated. The goal of this study is to evaluate immunohistochemical expression of L1 and L2 in SILs in correlation with lesion grade. One hundred fifty cervical specimens with SILs were selected based on HPV 16 or HPV 18 detection by Q-PCR. These included 89 low-grade SILs (LSIL/CIN1) and 123 high-grade SILs (75 HSIL/CIN2 and 48 HSIL/CIN3). More than one lesion/grade was identified in 53 specimens. The presence and grade of SIL was determined by a panel of pathologists. Capsid protein expression was assessed by immunohistochemistry using MAB 837 for L1 and RG-1 for L2. Lesions of different grades in the same specimen were scored separately. Expression of capsid proteins was detected in 34/89 (40%) LSIL/CIN1, 5/75 (6%) HSIL/CIN2 and none of 48 HSIL/CIN3. L1 and L2 were co-expressed in the same area of the lesion in 22 cases. In addition, L1 alone was expressed in 6 lesions and L2 alone in 11 lesions. Among the cases with multiple lesion grades in the same specimen, none with HSIL/CIN 3 expressed capsid proteins in any portion/grade of the lesion. HPV capsid proteins are expressed almost exclusively in LSIL/CIN1 and rarely in HSIL/CIN 2. Additional studies are warranted to examine lack of L1 and L2 expression in LSIL/CIN1 as a predictor of persistence or progression to HSIL/CIN 3, the precursor of cervical cancer.

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Section: Discussionmentioning

confidence: 99%

“…The inability to detect L1 in these LSIL/CIN 1 cases may reflect inadequate sampling, given the extremely focal staining in some cases noted in this and other studies. (22) Using cytology Pap samples likely provide a more representative sample of superficial lesional cells for analysis of L1 expression.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical detection of human papillomavirus capsid proteins L1 and L2 in squamous intraepithelial lesions: potential utility in diagnosis and management

et al. 2013

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“…[16][17][18][19][20][21][22] An ineffective immune response may be promoted by factors contributing to cervical cancer such as tobacco smoking or the coexistence of dysplasias of different grades (CIN1/CIN2) in the transformation zone, possibly reflecting a mixture of L1-positive and L1-negative lesions with different progressive potentials may be the reason for a progression of some of these L1-positive intraepithelial lesions.…”

Section: Discussionmentioning

confidence: 99%

HPV L1 detection discriminates cervical precancer from transient HPV infection: a prospective international multicenter study

et al. 2013

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The benefits of cytology-based cervical cancer screening programs in reducing morbidity and mortality are well recognized. Especially, overtreatment of human papillomavirus (HPV) high-risk positive early dysplastic lesions may have a negative impact on reproductive outcomes for fertile women. To optimize the clinical management an objective standard is needed to distinguish precancer that requires treatment, from spontaneously resolving HPV infections. In the current study, we examined the prognostic relevance of HPV-L1 capsid protein analysis with Cytoactiv in an international prospective multicenter study including 908 HPV high-risk positive early dysplastic lesions (LSIL/HSIL) during a follow-up period of 54 months. The clinical end points of the study were histologically confirmed CIN3 þ as progression, CIN1/2 for stable disease and repeated negative Pap smears as spontaneous clinical remission. The difference of the clinical outcome of HPV-L1-negative and HPV-L1-positive cases was statistically highly significant (P-valueo0.0001) independent of the classification as mild dysplasia (LSIL) and moderate dysplasia (HSIL). Of the HPV-L1-negative HPV high-risk positive mild/moderate dysplasias 84% progressed to CIN3, as compared with only 20% of the HPV-L1-positive cases. The data from our study show that HPV-L1 detection allows to identify transient HPV infections and precancerous lesions within the group of HPV high-risk positive early dysplastic lesions. The high progression rate of HPV-L1-negative mild and moderate dysplasia emphasizes the precancerous nature of these lesions. A close follow-up with colposcopy and histological evaluation is advisable and removal of these lesions should be considered. The low malignant potential of HPV-L1-positive cases, however, indicates transient HPV infection, justifying a watch and wait strategy with cytological follow-up, thus preventing overtreatment especially for women in their reproductive age. Modern Pathology (2013) 26, 967-974;

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“…Hilfrich / Hariri Using 101 HPV High risk positive CIN1 Choi et al [29] published 2010 that the HPV L1 protein expression is closely related to spontaneous disease regression. Not using p16, but a typespecific HPV-DNA Chip, it was possible for the first time to correlate the HPV type with the regression of the L1 positive CIN1 lesions.…”

Section: Risk Profilementioning

confidence: 99%

HPV L1 Detection as a Prognostic Marker for Management of HPV High Risk Positive Abnormal Pap Smears

Hilfrich¹

2013

Human Papillomavirus and Related Diseases From Bench to Bedside a Diagnostic and Preventive Perspective

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Human Papillomavirus L1 Capsid Protein and Human Papillomavirus Type 16 as Prognostic Markers in Cervical Intraepithelial Neoplasia 1

Abstract: The HPV L1 protein expression is closely related to spontaneous disease regression, but HPV-16 infection is related to persistent disease or progression to high-grade lesions in patients with CIN1.

Cited by 22 publications

References 19 publications

Immunohistochemical detection of human papillomavirus capsid proteins L1 and L2 in squamous intraepithelial lesions: potential utility in diagnosis and management

Immunohistochemical detection of human papillomavirus capsid proteins L1 and L2 in squamous intraepithelial lesions: potential utility in diagnosis and management

HPV L1 detection discriminates cervical precancer from transient HPV infection: a prospective international multicenter study

HPV L1 Detection as a Prognostic Marker for Management of HPV High Risk Positive Abnormal Pap Smears

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