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

MedStar author(s):
Citation: Modern Pathology. 26(2):268-74, 2013 Feb.PMID: 22996373Institution: MedStar Washington Hospital CenterDepartment: PathologyForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., ExtramuralSubject headings: *Alphapapillomavirus/me [Metabolism] | *Capsid Proteins/me [Metabolism] | *Carcinoma, Squamous Cell/di [Diagnosis] | *Cervical Intraepithelial Neoplasia/di [Diagnosis] | *Oncogene Proteins, Viral/me [Metabolism] | *Uterine Cervical Dysplasia/di [Diagnosis] | *Uterine Cervical Neoplasms/di [Diagnosis] | Carcinoma, Squamous Cell/pa [Pathology] | Carcinoma, Squamous Cell/vi [Virology] | Cervical Intraepithelial Neoplasia/pa [Pathology] | Cervical Intraepithelial Neoplasia/vi [Virology] | Female | Humans | Uterine Cervical Dysplasia/pa [Pathology] | Uterine Cervical Dysplasia/vi [Virology] | Uterine Cervical Neoplasms/pa [Pathology] | Uterine Cervical Neoplasms/vi [Virology] | Vaginal SmearsYear: 2013ISSN:
  • 0893-3952
Name of journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, IncAbstract: While cervical cancer screening relies on cervical cytology and high-risk human papillomavirus (HPV) detection, the 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, whereas 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. A total of 150 cervical specimens with SILs were selected based on HPV 16 or HPV 18 detection by Q-PCR. These included 89 low-grade SILs (LSIL/CIN 1) and 123 high-grade SILs (75 HSIL/CIN 2 and 48 HSIL/CIN 3). 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/CIN 1, 5/75 (6%) HSIL/CIN 2 and none of 48 HSIL/CIN 3. 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/CIN 1 and rarely in HSIL/CIN 2. Additional studies are warranted to examine lack of L1 and L2 expression in LSIL/CIN 1 as a predictor of persistence or progression to HSIL/CIN 3, the precursor of cervical cancer.All authors: Gravitt PE, Ogurtsova A, Roden RB, Ronnett BM, Rositch AF, Seidman J, Yemelyanova AFiscal year: FY2013Digital Object Identifier: Date added to catalog: 2013-09-17
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Journal Article MedStar Authors Catalog Article 22996373 Available 22996373

While cervical cancer screening relies on cervical cytology and high-risk human papillomavirus (HPV) detection, the 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, whereas 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. A total of 150 cervical specimens with SILs were selected based on HPV 16 or HPV 18 detection by Q-PCR. These included 89 low-grade SILs (LSIL/CIN 1) and 123 high-grade SILs (75 HSIL/CIN 2 and 48 HSIL/CIN 3). 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/CIN 1, 5/75 (6%) HSIL/CIN 2 and none of 48 HSIL/CIN 3. 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/CIN 1 and rarely in HSIL/CIN 2. Additional studies are warranted to examine lack of L1 and L2 expression in LSIL/CIN 1 as a predictor of persistence or progression to HSIL/CIN 3, the precursor of cervical cancer.

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