Type Specific Persistence of High Risk Human Papillomavirus (HPV) as Indicator of High Grade Cervical Squamous Intraepithelial Lesions in Young Women: Population Based Prospective Follow Up Study

Human papillomavirus (HPV) is one of the most common STDs. Although most infections are transient, the potential health implications are obvious because HPV types 16 and 18 are considered carcinogenic, and other types have an important role in cervical carcinogenesis. Most epidemiological evidence originates from cross sectional studies with samples from women taken after the cancer or the squamous intraepithelial lesion was diagnosed. Only few prospective cohort studies with reliable and sensitive methods for HPV testing have assessed the risk of new development of cervical neoplasia by using repeated measurements of genital HPV in their study design. Only in such studies can the temporal association between exposure and outcome be evaluated and established. However, the currently available studies included only a few women with high grade squamous intraepithelial lesions.

The authors of the current report carried out a prospective follow-up study to investigate the role of HPV in the development of cervical neoplasia in women who had no previous diagnosis of cytological abnormalities. The authors examined whether the presence of viral DNA can predict development of lesions. The authors also investigated the role of repeated detection of high risk compared with low risk types and repeated detection of the same virus compared with different types.

The authors collected a random sample of 17,949 women ages 20 to 29 from the general population of Copenhagen using the central personal registry (CPR). Every citizen in Denmark has a unique 10-digit CPR identification number that is universally used in the public administration. The authors invited all eligible women to a study clinic established at one of the university hospitals in Copenhagen. Recruitment was from May 1991 to January 1993. All of the 11,088 women in the study gave informed consent.

At enrollment, all 11,088 women were interviewed personally by specially trained female nurses. The nurses collected data on demographic variables, smoking, reproductive background, contraception, sexual habits, previous STDs, and history of cervical smear tests. The participants also had a gynecological examination, in which the authors carried out a smear test and obtained endo-ectocervical cells for detection of HPV DNA. In addition, all participants gave two blood samples. In October 1993, the authors invited the entire cohort for a second examination. During the following 18 months, 8,656 women (78 percent) underwent the second examination. Women were interviewed about suspected risk factors for cervical cancer, focusing on the time between enrollment and follow up. The authors did a smear test and took cervical swabs for HPV testing and two blood samples from each woman.

The authors also had the cohort under passive surveillance for occurrence of abnormal cytology. In November 1995 the authors linked the original cohort of 11,088 women to the pathology register files, and all women were traced in the register. By means of the pathology register the authors were able to get information about all such examinations on every woman in the study since their first smear test and up to the date of the register linkage. The authors excluded women with a history or current evidence of cervical neoplasia. After all exclusions, 10,177 women remained in the follow up study.

Compared with women who were negative for HPV at enrollment, those with positive results had a significantly increased risk at follow up of having atypical cells, low grade lesions or high grade lesions. Similarly, women who were positive for HPV at the second examination had a strongly increased risk of low and high grade lesions. For high grade lesions, the risk was strongly increased if the same virus type was present at both examinations. The association between persistence and high grade cervical lesions was more pronounced among women over 25.

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