Introduction of Human Papillomavirus DNA Screening in the World: 15 Years of Experience

Abstract

The discovery of the necessary cause of cervical cancer, human papillomavirus (HPV), has led to important technological advances, including the development of molecular tests for HPV to identify women with cervical precancerous lesions. HPV testing has proven to be more sensitive and more reliable, albeit less specific, for detection of cervical precancer than cytologic methods of detection. As the result, HPV testing can reduce the incidence of cervical cancer within 4–5 years and reduce the mortality due to cervical cancer within 8 years compared to cytology. Additionally, a negative HPV test provides greater reassurance against cervical cancer than a negative Pap test. HPV testing, because of its attributes, is useful for screening out low-risk women who do not need further intervention for 5 or more years. Thus, HPV testing can shift the emphasis of the use of Pap testing or any other more specific diagnostic test from frequent use in the entire population to the ∼10% subset of women who tested positive for the causal factor, HPV. Here, we highlight the current and future status of the introduction of HPV testing into routine cervical cancer screening.

This article forms part of a special supplement entitled “Comprehensive Control of HPV Infections and Related Diseases” Vaccine Volume 30, Supplement 5, 2012.

Introduction

For over 50 years, cervical cytology, first using the conventional Pap smear and more recently liquid-based cytologic methods, has been the standard of care for cervical cancer screening [1]. Where cytology-based programs have been launched effectively, annual rates of cervical cancer have been reduced by 50–90%. These programs require training, the development of laboratory infrastructure, standardization, and quality control measures. While there are no clinical trials to establish a direct evidential link between cytology and the reduction of cancer incidence, there is little dispute that cytology-based screening and timely follow-up of screen positives for the diagnosis and treatment of precancerous lesions has been the cause for these reductions in cervical cancer incidence.

As discussed elsewhere in this Monograph, there is now substantial and consistent evidence that HPV DNA detection has 20–45% greater one-time test sensitivity for precancer and early cancer of the cervix (cervical intraepithelial neoplasia [CIN]3+) than cytology-based methods [2], [3], [4], [5], [6], [7], [8]. Importantly, these precancerous lesions (CIN3 and perhaps CIN2) found by HPV testing and missed by cytology are clinically important: a single round of HPV-based screening more effectively reduces the incidence of cervical cancer within 4–5 years [5], [7] and cancer-related mortality within 8 years [9] than does a single round of cytology-based screening. Consequently, HPV DNA testing is now being introduced into some countries as an adjunct to cytology screening (“co-testing”) or as the primary screening test to be followed by a secondary, more specific test, such as cytology. We present some examples where HPV DNA is being considered as the primary test for cervical cancer screening.