ReviewIntroduction of Human Papillomavirus DNA Screening in the World: 15 Years of Experience
Highlights
► We review the rationale for using HPV testing in routine cervical screening. ► We discuss the advantages and disadvantages of primary cervical cancer screening with HPV testing alone versus HPV and cytology co-testing or cytology testing alone. ► We highlight the introduction of HPV testing in several countries. ► We discuss the possibilities and challenges of introducing HPV testing for cervical cancer screening in lower-resource settings.
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.
Section snippets
United States of America
The United States of America (USA) was an early adopter of HPV testing in the screening and management of women undergoing cervical cancer screening. In 2001, primarily based on the strength of evidence from the Atypical Squamous Cells of Undetermined Significance (ASCUS) Low-Grade Intraepithelial Lesion (LSIL) Triage Study (ALTS) [10] reflex HPV testing for the triage of equivocal (ASC-US) cytology was recommended [11].
Since the United States (U.S.) Food and Drug Administration (FDA) approval
Acceptance of HPV testing
There are limited studies to assess the psychosocial impact and acceptability of introducing HPV testing on women. A recent review of the evidence found that women preferred reflex test by HPV testing and referral of HPV-positive women to colposcopy rather than repeat cytology for management of their borderline and low-grade cytology. In contrast, the same review found that there was a slight preference for cytology over HPV testing (with hypothetical management algorithms) for screening the
Final comments
Although HPV vaccines may represent the ultimate cervical cancer prevention modality, especially if the next generation of HPV vaccines that target seven HPV genotypes proves effective over a long duration, they will not greatly benefit the next generation or two that have already been exposed to causal HPV infections and some of whom have or will develop cancer [38]. Certainly the first important benefit to be realized will be a reduction of pre-invasive lesions and a multitude of unimportant
Disclosed potential conflicts of interest
PEC: Serves as a member of a Data and Safety Monitoring Board to review data on HPV vaccines for Merck and has received HPV test reagents and testing for research from Qiagen and Roche at a reduced or no cost.
JLB: Has received support in kind (reagents and testing) and funds for direct support and research, under the auspices of Preventive Oncology International Inc., from Hologic Inc., Qiagen, Gen-Probe, Merck Inc., and BGI Shenzhen.
EL-P: Received HPV tests at reduced and at no cost from
Acknowledgements
The views expressed in this document are solely of the authors and do not reflect the views of the American Society for Clinical Pathology or any other organization. The work was partially supported by public grants from the European Commission (7th Framework Programme grant HEALTH-F3-2010-242061, PREHDICT), from the Instituto de Salud Carlos III (Spanish Government) (grants FIS PI10/02995, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095 and CIBERESP) and from the Agència de Gestió d’Ajuts
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