Balkan Journal of Medical Genetics

Although cervical screening based on cytology is effective in decreasing the incidence of and mortality from cervical cancer, it has limitations. Thus, in a meta-analysis of 62 studies of cytological screening conducted between 1984 and 1992, the mean sensitivity of the method was 58% (range = 11-99%) and its mean specificity was 68% (range = 14-97%) [18]. Relative proportion of sampling to screening errors was estimated to be about 2:1 in conventional cytology [18]. Recent evidence indicates that results for cytological screening could be improved by the adoption of liquid-based cytology (LBC). Implementation of LBC techniques is being encouraged in the UK and in the USA [19]. However, the relative insensitivity of cytology means that frequent testing is required for optimal cancer protection. The most cost-effective approach in cervical cancer screening programs would be to use the most sensitive possible test at the longest possible interval between screenings. Using HPV testing instead of, or in combination with cytology, will indeed permit longer intervals between screenings and with similar efficiency as repeated cytology for the detection of precursor cervical lesion [20].

The primary advantage of HPV testing is its negative predictive value [20,21]. Evidence indicates that HPV testing for primary screening is at least as efficient as conventional cytology testing and is superior to repeated cytology in the triage of unequivocal smears. For HPV-induced cervical precancerous lesions, a minimum screening age of 25 years, or 8 years from first intercourse, is indicated. Because HPV infection is very common in women under the age of 30, it would be more appropriate for HPV testing to be offered to women older than 30. In women with a negative HPV test and a normal cytology, the screening interval can safely be extended to 8-10 years without compromising cancer prevention. However, in countries where annual or biennial cytological screening is usual, the screening intervals of 3-5 years of HPV and cytological testing would be more acceptable to be adapted [21].

Human papillomavirus testing was proposed by the American Society for Colposcopy and Cervical Pathology (ASCCP) for the management of women with cervical cytological abnormalities [22]. Human papillomavirus testing was also included in the Croatian diagnostic and therapeutic guidelines for pre-malignant cervical lesions [23]. Basically, in both guidelines, HPV testing has been used as a screening test together with cytology for women 30 years of age or older, and as a follow-up test for women with minor cervical abnormalities and for women after treatment of major cervical abnormalities. The number of women who have been offered HPV testing from 1996 until now in Croatia is sporadic and underestimated, making it impossible to measure the benefit of HPV testing on the cervical cancer incidence and mortality rates. This would be possible only if HPV testing is included in the cervical cancer screening program, that is missing in Croatia as well as in most countries from the Former Yugoslavia. Although HPV testing has not been approved for cervical cancer screening programs anywhere in Europe, its use is under evaluation in several developed countries.

The HPV test consists of detection of the viral genome by the extremely specific and sensitive methods based on DNA and/or RNA hybridization and/or amplification by PCR [24,25]. Most methods are used in the research setting and only a few HPV tests are commercially available and approved for clinical application. In general, the HPV DNA test has to be reproducible, easy to perform and cost-effective for clinical diagnosis. Only the hybrid capture second-generation HPV DNA test (HC2; Digene Co., Gaithersburg, MD, USA) and the PCR-enzyme immunoassay (EIA)-based HPV DNA test (Roche Molecular Systems, Alameda, CA, USA) that recognize 13 HR HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) are recommended for large-scale clinical use.