Abstract | HPV je mali DNK virus, veličine genoma oko 8000 parova baza. Poznato je oko 200 različitih tipova virusa, a oko 40 tipova uzrokuje infekciju epitela anogenitalne regije u ljudi. Visokorizični tipovi koji se povezuju s intraepitelnim lezijama i genitalnim karcinomima su sljedeći: 16,18,31,33,35,39,45,51,52,56,58,59,68,73,82.
HPV je najčešća spolno prenosiva bolest i smatra se da više od 75% žena u nekom trenutku u životu dođe u kontakt s virusom. Više od 90% inficiranih žena uspostavi učinkovit imunološki odgovor i infekcija nestaje spontano unutar 24 mjeseca od početka, bez ikakvih ozbiljnijih posljedica. Iako infekcija bilo kojim visokorizičnim tipom virusa može uzrokovati cervikalnu intraepitelnu leziju (CIN), to se najčešće sprječava liječenjem HPV infekcija. Perzistentne i ponavljajuće infekcije HPV-om uzrok su intraepitelne neoplazije i karcinoma vrata maternice. Infekcija HPV-om uzrok je karcinoma vrata maternice u više od 99% slučajeva, širom svijeta.
U razvijenim zemljama program probira (screening) na rak vrata maternice, provodi se od sredine 1950-ih godina. Metoda prvog izbora je Papa-test za detekciju prekursora karcinoma cerviksa. Iako je to drastično smanjilo stopu smrtnosti od karcinoma vrata maternice, interpretacija Papa-testa zahtjeva visoku edukaciju i izvježbanost citoskrinera pa su česti lažno negativni rezultati. Iako su citološke promjene u razmazu Papa-testa primarno uzrokovane HPV infekcijom, neke upale ili nepravilno uzeti uzorci mogu rezultirati lažno pozitivnim nalazom. Nakon patološkog nalaza Papa testa potrebno je ponoviti nalaz Papa-testa, uraditi HPV testiranje, napraviti kolposkopiju i biopsiju.
Detekcija nukleinskih kiselina PCR tehnikom neinvazivna je metoda detekcije prisutne HPV infekcije spolnog sustava. Uvođenje molekularnih metoda detekcije HPV infekcije poboljšalo je i unaprijedilo screening programe. Na taj način omogućena je ranija detekcija visokorizičnih lezija. Nadalje, detekcijom pojedinačnih tipova HPV 16 i 18 kao najčešćih uzročnika karcinoma, omogućeno je selektiranje kandidatkinja za kolposkopiju, te je u konačnici smanjen broj nepotrebnih kolposkopija.
S obzirom na visoku osjetljivost, molekularne metode detekcije HPV-a nameću se kao prvi izbor u programima probira, te je zbog toga PCR predložen i usvojen u mnogim screening programima kao primarni test probira. |
Abstract (english) | Human papillomavirus is a small, double-stranded DNA virus, with a genome of approximately 8000 nucleotides. There are more than 200 different types of HPV, and approximately 40 different HPVs that can infect the anogenital mucosa. Next types are considered high-risk for development of CIN (cervical intraepithelial neoplasia) and cervical cancer: 16,18,31,33,35,39,45,51,52,56,58,59,68,73,82.
Sexually transmitted HPV infection is extremely common, with estimates of up to 75% of all women experiencing exposure to HPV at some point of life. However, > 90% of infected women will develop an effective immune response and they will clear the infection in 24 months without any long term health consequences. Infection with any high-risk HPV type can produce CIN. HR-HPV infections are self-limited and regress spontaneously within several months. Persistent HPV infection is the cause of cervical cancer and its precursor cervical intraepithelial neoplasia (CIN). The presence of HPV has been implicated in more than 99% of cervical cancers, worldwide.
In developed countries with cervical cancer screening programs, the Pap smear has been used since the mid-1950s as the primary tool to detect early precursors to cervical cancer. Although it decreased the mortality rates due to cervical cancer dramatically in those countries, the Pap smear requires interpretation by highly trained cytopathologists and is a relatively inaccurate test with a high rate of false negative results. Cytological abnormalities observed in the Pap smear are primarily due to infection with HPV, however, various inflammatory or sampling variations can result in false positive Pap result. Triage of an abnormal Pap smear involves repeated Pap smear testing, HPV DNA testing, colposcopy and biopsy.
Nucleic acid (DNA) testing by PCR is non-invasive method for determining the presence of a cervical HPV infection. The implementation of HPV DNA testing has increased the efficiency of cervical cancer screening programs by detecting high-risk lesions earlier. Furthermore, by detecting individual HPV types 16 and 18 as the most common carcinogenic agent, candidates for colposcopy selection were disabled and ultimately reduced the number of unnecessary colposcopy.
With superior sensitivity established, HPV DNA testing as a first-line primary screening test has been proposed and adopted in some screening programs. |