Uporaba testov HPV DNK za presejanje za raka materničnega vratu Use of the HPV DNA test for cervical cancer screening

Abstract

Okužba z onkogenimi tipi humanih papilomavirusov (HPV) je potreben pogoj za razvoj raka materničnega vratu. Zaradi dolgoletne uporabe citoloških brisov se je incidenca tega raka zmanjšala, a kljub temu bi bilo treba najti nov presejalni test, ki bi bil občutljivejši za progresivne predrakave spremembe, cervikalno intraepitelialno neoplazijo (CIN). Med te teste spadajo testi HPV DNK. V tem članku so opisane njihove značilnosti, kakor jih je mogoče presoditi na podlagi vseh 8 randomiziranih kontroliranih raziskav z objavljenimi podatki, ki so primerjale uporabo testov HPV s citološkimi brisi za primarno presejanje. Te raziskave so potrdile, da je mogoče na podlagi testov HPV diagnosticirati večje število ≥ CIN 3 kot na podlagi citoloških brisov, čeprav razlika v nekaterih od raziskav, tudi zaradi njihove velikosti, ni bila statistično značilna. Razveseljivo je, da večja občutljivost za ≥ CIN 3 verjetno pomeni tudi boljšo zaščito pred rakom materničnega vratu, čeprav ocena temelji na majhnem številu opazovanih primerov v vsaki izmed raziskav. Pri uporabi testov HPV bo večji izziv omejiti njihove neželene učinke. To so predvsem pogostejši napačno pozitivni testi (ki jih definiramo kot pozitivne presejalne teste brez diagnoze ≥ CIN 3 ali ≥ CIN 2) ter pogostejše diagnoze in morebitno zdravljenje manj nevarnih stopenj CIN (predvsem CIN 1, deloma tudi CIN 2). V tem članku so kritično ovrednoteni 3 pristopi k zmanjšanju bremena testov HPV v primerjavi s citološkimi brisi, in sicer uporaba triažnih testov pri ženskah s pozitivnimi presejalnimi testi HPV, omejitev uporabe testov HPV pri mlajših ženskah in sprememba mejne vrednosti, pri kateri se test HPV odčita kot pozitiven. Vsi ti pristopi imajo svoje prednosti in slabosti.

Abstract (Eng)

An infection with oncogenic types of Human Papillomavirus (HPV) is a necessary condition for development of cervical cancer. The incidence of cervical cancer has decreased over the years in line with the use of cytology screening. Nevertheless, cytology is not an optimally sensitive screening test for cervical intraepithelial neoplasia (CIN), and a more sensitive test would be beneficial. The aim of this paper was to describe the characteristics of HPV DNA tests as observed in all eight randomized controlled trials with published data that compared HPV tests and cytology in primary screening. These trials showed that the sensitivity of HPV tests for ≥CIN3 is higher than the sensitivity of cytology. In several trials, the higher sensitivity in the baseline screening rounds led to fewer diagnoses of cervical cancer by the subsequent screening round than was the case with cytology, although these observations were based on few cases per trial. It will be a greater challenge to limit the amount of extra unwanted side effects of HPV testing compared with cytology. These are predominantly false-positive tests, i.e. positive screening tests without a subsequent diagnosis of ≥CIN3, and extra diagnoses of CIN grades with a low probability of progression to cervical cancer, i.e. CIN1 and to some degree also CIN2. The three most widely discussed approaches to reducing the burden of the extra unwanted effects were discussed in this paper: the use of triage tests in women with positive HPV screening tests, the use of HPV tests from the age of 30 years onwards only, and a change in the threshold value for a positive HPV test. Each of these approaches is associated with distinct advantages and disadvantages.