The epidemiology of cervical cancer indicates that some sexually transmitted agent is responsible and Human papillomavirus (HPV) is the currently favoured agent. This study was designed to assess whether HPV 16 could be identified by filter in-situ hybridisation (FISH) in the normal cervix and, if present, whether the woman was placed at an increased risk of developing cervical neoplasia. To examine this question, 1412 women, attending for routine cervical cytology, were studied. HPV 16 DNA was found in the cervical scrapes in 23% of this population when assayed by FISH. There was no difference in the positivity rates between those with normal or abnormal cytology. A group of women (427) from this cohort, who were all cytologically normal, were colposcoped and a significant association between cervical disease, missed by cytology, and HPV16 positivity was found (p = 0.01). A follow-up case control study of those with a normal cervix with or without HPV16 DNA was conducted. Regular review over the ensuing 2 years with repeat cytology, colposcopy and FISH was undertaken. Only nine of these women developed any evidence of CIN over this period and this was not associated with HPV16 DNA. The epidemiologic factors were also compared between the cases and the controls. 162 cervical scrapes were used to compare the FISH method with Southern blotting and a weak association was found (Kappa=0.32), indicating the limitations of FISH for this type of study. The serial FISH results from each colposcopy clinic visit were assessed and also showed weak association
