Genital warts and cervical cancer. III. Subclinical papillomaviral infection and cervical neoplasia are linked by a spectrum of continuous morphologic and biologic change

R. Reid, C. P. Crum, B. R. Herschman, Y. S. Fu, L. Braun, K. V. Shah, S. J. Agronow, C. R. Stanhope

Research output: Contribution to journalArticle

Abstract

Human papillomaviral (HPV) infection is now widely advanced as an important etiologic factor in cervical cancer. This study was undertaken to clarify morphologic relationships within the biologic spectrum linking subclinical papillomaviral infection (SPL) to cervical intraepithelial (CIN). Two pathologists analyzed 72 colposcopic biopsies, using a semi-objective rating scheme that scored 24 different histologic criteria. Each individual criterion was checked for reproducibility, and validated against an objective measure of papillomaviral infection (immunoperoxidase staining) or premalignant change (microspectrophotometry). The individual criteria were then combined into histologic indices of benign warty change, presumed viral atypia, abnormal cell phenotype, and disturbed tissue maturation. Histologic expression of papillomaviral infection decreased with increasing degrees of premalignant change. Plotting the index of abnormal cell phenotype against that of disturbed tissue maturation produced a linear plot in which cases clustered into four diagnostic groups. The histiologic indices of papillomavirus infection displayed significant curvilinear correlations with genotypic distortion, benign warty change being maximal in the CIN 1 range and presumed viral atypia in the CIN 2 range. Disturbance of nuclear DNA content also increasing with worsening diagnosis; diploidy being most common in SPI (67%), polyploidy in CIN 1 (59%), and aneuploidy in CIN 2 (65%) and CIN 3 (82%). Conversely, capsid antigen production decreased from 36% in SPI to 9% in CIN 3. Three aneuploid epithelia were immunoperoxidase positive. These inverse relationships between late viral expression and nuclear distortion fit experimental models of viral oncogenesis. The gradual transition and morphologic overlap between diagnostic groups support the postulate that SPI and CIN are a single disease spectrum, in which differences are those of degree rather than of kind.

Original languageEnglish (US)
Pages (from-to)943-953
Number of pages11
JournalCancer
Volume53
Issue number4
StatePublished - 1984

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Condylomata Acuminata
Asymptomatic Infections
Uterine Cervical Neoplasms
Aneuploidy
Infection
Microspectrophotometry
Phenotype
Neoplasms
Polyploidy
Papillomavirus Infections
Capsid
Diploidy
Carcinogenesis
Theoretical Models
Epithelium
Staining and Labeling
Biopsy
Antigens
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Reid, R., Crum, C. P., Herschman, B. R., Fu, Y. S., Braun, L., Shah, K. V., ... Stanhope, C. R. (1984). Genital warts and cervical cancer. III. Subclinical papillomaviral infection and cervical neoplasia are linked by a spectrum of continuous morphologic and biologic change. Cancer, 53(4), 943-953.

Genital warts and cervical cancer. III. Subclinical papillomaviral infection and cervical neoplasia are linked by a spectrum of continuous morphologic and biologic change. / Reid, R.; Crum, C. P.; Herschman, B. R.; Fu, Y. S.; Braun, L.; Shah, K. V.; Agronow, S. J.; Stanhope, C. R.

In: Cancer, Vol. 53, No. 4, 1984, p. 943-953.

Research output: Contribution to journalArticle

Reid, R, Crum, CP, Herschman, BR, Fu, YS, Braun, L, Shah, KV, Agronow, SJ & Stanhope, CR 1984, 'Genital warts and cervical cancer. III. Subclinical papillomaviral infection and cervical neoplasia are linked by a spectrum of continuous morphologic and biologic change', Cancer, vol. 53, no. 4, pp. 943-953.
Reid, R. ; Crum, C. P. ; Herschman, B. R. ; Fu, Y. S. ; Braun, L. ; Shah, K. V. ; Agronow, S. J. ; Stanhope, C. R. / Genital warts and cervical cancer. III. Subclinical papillomaviral infection and cervical neoplasia are linked by a spectrum of continuous morphologic and biologic change. In: Cancer. 1984 ; Vol. 53, No. 4. pp. 943-953.
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abstract = "Human papillomaviral (HPV) infection is now widely advanced as an important etiologic factor in cervical cancer. This study was undertaken to clarify morphologic relationships within the biologic spectrum linking subclinical papillomaviral infection (SPL) to cervical intraepithelial (CIN). Two pathologists analyzed 72 colposcopic biopsies, using a semi-objective rating scheme that scored 24 different histologic criteria. Each individual criterion was checked for reproducibility, and validated against an objective measure of papillomaviral infection (immunoperoxidase staining) or premalignant change (microspectrophotometry). The individual criteria were then combined into histologic indices of benign warty change, presumed viral atypia, abnormal cell phenotype, and disturbed tissue maturation. Histologic expression of papillomaviral infection decreased with increasing degrees of premalignant change. Plotting the index of abnormal cell phenotype against that of disturbed tissue maturation produced a linear plot in which cases clustered into four diagnostic groups. The histiologic indices of papillomavirus infection displayed significant curvilinear correlations with genotypic distortion, benign warty change being maximal in the CIN 1 range and presumed viral atypia in the CIN 2 range. Disturbance of nuclear DNA content also increasing with worsening diagnosis; diploidy being most common in SPI (67{\%}), polyploidy in CIN 1 (59{\%}), and aneuploidy in CIN 2 (65{\%}) and CIN 3 (82{\%}). Conversely, capsid antigen production decreased from 36{\%} in SPI to 9{\%} in CIN 3. Three aneuploid epithelia were immunoperoxidase positive. These inverse relationships between late viral expression and nuclear distortion fit experimental models of viral oncogenesis. The gradual transition and morphologic overlap between diagnostic groups support the postulate that SPI and CIN are a single disease spectrum, in which differences are those of degree rather than of kind.",
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