Histological and immunocytochemical study of cervical intraepithelial neoplasia (CIN) with associated HPV 6 and HPV 16 infections.

Abstract

SUMMARY Histological and immunocytochemical features of cervical intraepithelial neoplasia (CIN) associated with HPV 6 and HPV 16, either singly or in combination, were studied in 48 cases. Features of HPV infection (koilocytosis, binucleation, multinucleation, giant irregular nuclei and individual cell dyskeratosis) were present in high prevalence in both HPV 6 and HPV 16 associated CIN. Abnormal mitoses seemed to be a good indicator of.CIN and were present in about 50% of cases of CIN associated with either HPV 6 or HPV 16 infection. This finding provides no support for the view held by some investigators that associated HPV 16 infection can be predicted by the presence of abnormal mitoses. Expression of HPV antigen was shown in about 40% of cases with a slight, but not significantly, higher prevalence in cases of combined HPV 6 and HPV 16 infection. Conventional histology and immunocytochemistry could not distinguish CIN associated with HPV 6 from CIN associated with HPV 16 infection.Human papillomavirus (HPV), in particular HPV types 6, 11, 16, and 18, have been associated with the aetiology of cervical neoplasia.`3 HPV types 6 and 16 account for most HPV infection in the female lower genital tract in Great Britain,4 and they seem to have different tumorigenic potential. HPV type 6 is found most commonly in cervical condylomata acuminata and cervical intraepithelial neoplasia (CIN) of lower grades while HPV type 16 is associated with CIN of more severe grades1 S and invasive cancer.6Knowledge of the type of HPV associated with CIN in an individual patient might be of prognostic importance.To date, it has not been possible to grow HPV in culture. Typing is performed with the DNA-DNA hybridisation technique, which demands extensive technical experience and expertise. It would be advantageous if histological features could be identified to distinguish CIN associated with HPV type 6 from type 16 infection. Gross7 reported HPV type specific cytopathic effects recognisable on routine histology for HPV types 3, 4, and 6, and, in a small study Accepted for publication 29 May 1986 Crum8 suggested that the presence of HPV type 16 in cervical flat warts may be predicted by the presence of abnormal mitoses.The purpose of this study was to investigate if HPV type 6 and type 16 produce different and discriminatory cytopathic effects in CIN recognisable by conventional histology and to investigate the prevalence and pattern of the expression of HPV viral antigen in both types of infection. Material and methods STUDY GROUPPatients were drawn from a cohort of women attending a district colposcopy clinic who participated in a recent study of the prevalence of different types of HPV in the uterine cervix.5 Because of the lower prevalence of HPV type 6 in CIN, all the patients with HPV 6 DNA in their lesions were included in the study. Thirty patients were randomly selected from the group with HPV 16 DNA and another 10 patients with no HPV DNA sequences were also studied. In the study on HPV antigen expression a larger group...

Reactivities of Polyclonal and Monoclonal Antibodies Raised to the Major Capsid Protein of Human Papillomavirus Type 16

“…HPV-6 and -11 are associated with benign genital warts (condylomata acuminata) and low grade CIN (Gissmann et al, 1983) while HPV-16 and -18 are found infrequently in benign lesions but are present in all grades of CIN and in malignant disease of the cervix and penis (D/irst et al, 1983;Boshart et al, 1984;McCance, 1986). HPV is at present typed by genome homology using DNA-DNA hybridization, because the lack of an in vitro cell culture system means that sufficient amounts of viral antigens are not available for serological comparisons.…”

“…These tissue sections were incubated in 0-5~ iodine (in 70~ alcohol) for 5 min followed by treatment with 5 ~ sodium thiosulphate to remove the mercury. Immunoperoxidase staining was carried out using the ABC complex (Jenkins et al, 1986).…”

“…HPV types 6 and 11 are associated with benign condylomata acuminata (genital warts) (Gissmann et al, 1983;McCance et al, 1986) and low grade cervical intraepithelial neoplasia (CIN) (McCance et al, 1985) which is a premalignant lesion localized in the transformation zone of the cervix. HPV-16 and -18 (Dfirst et al, 1983;Boshart et al, 1984) are the commonest viruses associated with all grades of CIN (grades I to III) and with malignant carcinoma of the cervix.…”

“…HPV-16 and -18 (Dfirst et al, 1983;Boshart et al, 1984) are the commonest viruses associated with all grades of CIN (grades I to III) and with malignant carcinoma of the cervix. In addition HPV-16 has been shown to be associated with progression of mild CIN (grade I) to severe CIN (grade III) (Campion et al, 1986).…”

“…Type-specific antibodies have not been produced because these viruses as a group do not replicate and produce infectious virus in cell cultures, so quantities of virus particles sufficient for antibody production are not available. Antibodies raised against detergent-disrupted bovine papillomavirus type 1 (BPV-1) have been used to detect H PV antigens in tissues but these antibodies cross-react with most animal and human papillomaviruses and are not type-specific (Jenkins et al, 1986). There is a need for type-specific sera for diagnostic purposes since, in particular, HPV-16 is associated with progressive disease.…”