Persistence of human papillomavirus (HPV) infections preceding cervical carcinoma

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Abstract
BACKGROUND A persistent genital infection with an oncogene‐type of human papillomavirus (HPV) is considered to be essential for the development of most cervical carcinomas. Therefore, HPV analysis has been proposed as a possible complementary cytological screening program. The authors have developed a technique to analyze archival Pap smears, which has enabled them to study the relation between persistent HPV infection and the development of cervical cancer. METHODS Nested polymerase chain reaction was used to demonstrate the presence of HPV DNA, and sequencing of the obtained amplimer was performed to establish HPV type. The authors analyzed a series of 88 smears taken 1.5 to 7 years prior to the diagnosis of an HPV‐containing cervical carcinoma (12 invasive adenocarcinomas, 18 invasive squamous carcinomas, and 58 squamous carcinoma in situ), which were compared with age‐matched controls with no tumor development. RESULTS HPV DNA was present in a majority of the smears preceding a cancer, with an odds ratio of around 15 for all tumor groups. Infections with a persisting HPV type were demonstrated in most samples from a series of eight patients, from who multiple smears were available, covering the 7‐year period preceeding the cancer diagnosis. CONCLUSIONS Persisting infection can be demonstrated in exfoliated cells many years before cancer is diagnosed. The results are complementary to those obtained with cytology, that is, HPV is detected also in those at‐risk patients whose Pap smears are morphologically normal. However, the results are still insufficient to justify a general recommendation to use HPV testing for health control purposes. Cancer 1996;77:121‐7.