https___www.std.uw.edu_go_pathogen-based_hpv_core-concept_all.xml
http___fiziodermcentar.com_index.php_usluge_dermatologija_lijecenje-hpv-infekcije_1.xml
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Background Human papillomavirus (HPV) is one of the most common sexually transmitted infections (STIs). More than 170 types of HPV have been classified and more than 40 types of HPV can infect the genital tract of humans.[1,2,3] Genital HPV types are divided into two groups based on whether they have an association with cancer. Infections with low-risk types (non-oncogenic) are not associated with cancer but can cause genital warts and benign or low-grade cervical cellular changes. Infections with high-risk types (oncogenic), most notably HPV types 16 and 18, can cause low-grade cervical cellular changes, high-grade cervical cellular changes (moderate to severe Pap test abnormalities), and cancer of the cervix; in addition, some high-risk HPV types have been associated with cancers of the vulva, vagina, anus, penis, and oropharynx.[4] Most HPV infections, whether caused by low-risk or high-risk types, are transient, asymptomatic, and have no clinical consequences. Estimates on the incidence and prevalence of HPV infection are limited because HPV infection is not a reportable infection in any state (genital warts are reportable in a select number of states). In addition, most HPV infections are asymptomatic or subclinical, and therefore not diagnosed. Available HPV-related data primarily focuses on the clinical sequelae of HPV infection, such as genital warts and genitourinary cancers. Incidence and Prevalence It is estimated that most sexually active men and women will acquire genital HPV infection at some point in their lives, but approximately 90% of these infections are clinically silent and most infections resolve spontaneously.[5] Because HPV is not a reportable disease in the United States, precise yearly statistics on the incidence (new HPV infections) are not available. However, the Centers for Disease Control and Prevention (CDC) estimates there are approximately 14.1 million new HPV infections in the United States each year.[6] More information is known regarding HPV prevalence (persons living with HPV infection), particularly based on data from the National Health and Nutrition Examination Survey (NHANES).[5] In the United States, an estimated 79 million women aged 14 to 59 years are infected with HPV, with the highest prevalence among those aged 20 to 24 years.[5,7] In addition, a substantial number of genitourinary cancers and anogenital warts are attributable to HPV infection. For example, in 2009, an estimated 35,000 new HPV-associated cancers and 355,000 new cases of anogenital warts were associated with HPV infection.[8,9] In the past decade, genital warts has consistently accounted for 300,000 or more visits to an out-patient health care facility (Figure 1).[5] In a separate analysis, the CDC estimated an average of 30,700 annual cancers attributable to HPV during the years 2008-2012, with approximately 60% of these cancers involving females.[10] Notably, in this CDC analysis, the rates of cervical carcinoma were higher among blacks than among whites, and among Hispanics than non-Hispanics.[10] In addition, higher rates of HPV-associated cancer were seen among persons living in the southern region of the Unites States compared with those living in other regions. Learning Question Impact of HPV Vaccine on HPV Prevalence The prevalence of infection with high-risk types has drastically decreased with the availability of effective HPV vaccines. A recent study analyzed 14 to 34 year-old females in the NHANES study group and compared rates of vaccine-targeted strains between the pre-vaccine era (2003-2006) and 4 years of the vaccine era (2009-2012).[11] This study demonstrated a 64% decrease in vaccine-targeted HPV prevalence among females aged 14 to 19 years and a 34% decrease among those aged 20 to 24 years; there was not a significant decrease in women aged 25 to 29 but only 14.7% had received the HPV vaccine (Figure 2).[12] These findings are somewhat dynamic as the number of types in the HPV vaccine used in the United States has expanded from 4 to 9.[13] Even without the expanded types in the HPV vaccine, the overwhelming trend is towards a decrease in the prevalence of infections by high-risk types of HPV in vaccinated populations. Impact of HPV Vaccine on HPV-Related Disease The availability of effective HPV vaccines has led to a decline in some but not all sequelae of HPV infections among women in the United States.[10,14] In a meta-analysis of 20 eligible studies, investigators showed that in countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased by 68% between the pre-vaccination and post-vaccination periods and anogenital warts decreased by 61% in girls 13-19 years of age.[15] In the United States, the prevalence trends for anogenital warts varies by age and sex (Figure 3). [16] Among females aged 15–19, HPV prevalance was stable during 2003–2007, but then significantly declined during 2007–2010.[16] Among females aged 20–24 years, anogenital wart prevalence significantly increased during 2003–2007, was stable during 2007–2010, then began to decrease during 2009–2010.[16] Prevalence in females 25-39 years of age (persons unlikely to have been vaccinated) significantly increased throughout the time period. For males aged 15-39 years, the anogenital wart prevalence for each 5-year age group increased from 2003-2009, but no increases were observed for 2010.[16] Rates of precancerous lesions declined following the introduction of HPV vaccination; an analysis of the New Mexico HPV Pap Registry from 2007-2014 showed significant declines in all stages of cervical intraepithelial neoplasia (CIN) for women aged 15-19 years.[17] Data from the CDC HPV-IMPACT Project, a sentinel surveillance project, also demonstrated dramatic declines in cervical precancer incidence from 2008-2012 for women aged 18-20 years, with some sites also demonstrating significant declines among women aged 21-29 years.[18] Of note, screening recommendations changed during this time period so declines in disease may reflect both reduced screening and impact of vaccination. During the same time there was a significant decline in prevalence of HPV 16- and 18-related precancer among adult women who received at least 1 dose of HPV vaccine.[19] Risk Factors Key risk factors associated with acquisition of genital HPV infection include higher number of sexual partners and lower education level.[20] Investigators have evaluated potential risk factors associated with cervical cancer, including oral contraceptives, multiple pregnancies, tobacco smoking, nutrition (vitamins C and E, carotenoids, xanthophylls), immunosuppression, prior herpes simplex virus 2 infection, or Chlamydia trachomatis infection. These factors may possibly play a secondary role in progression to cervical cancer, but none consistently demonstrate the same strength of association as seen with high-risk HPV infection. Cost In the United States, direct annual medical costs associated with genital HPV infection, including treatment of genital warts, precancers and cancers, and screening for cervical cancer, are estimated to be $1.7 billion.[5]
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Liječenje HPV infekcije Učestalost spolno prenosivih infekcija je visoka bez obzira na mogućnost uspješne dijagnostike i liječenja. Najugroženija je populacija spolno aktivnih osoba mlađih od 25 godina, koja čini 60% oboljelih. Mladi ljudi češće imaju više partnera, a skloni su neredovitoj uporabi mjera zaštite (neprimjena barijernih metoda, kondom), pri čemu su osobe ženskog spola zbog bioloških karakteristika sklonije infekciji. Način prijenosa HPV infekcije Spolno prenosive infekcije većinom se prenose spolnim odnosom. Označavaju prisutnost potencijalnog uzročnika u organizmu, a time i mogućnost prenošenja infekcije na seksualnog partnera. Velika mobilnost današnje populacije pridonosi proširenosti uzročnika. Uzročnici tih infekcija mogu biti bakterije (Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, Ureaplasma urealyticum, Mycoplasma hominis), paraziti (svrab, stidne uši), protozoi (Trichominas vaginalis) i virusi kao humani papillomavirus, virus hepatitisa B, herpes simplex, HIV (virus humane imunodeficijencije) koji od svih uzročnika nosi najozbiljnije posljedice. Infekcija humanim papilomavirusom (HPV) danas je najčešća virusom uzrokovana spolno prenosiva infekcija. Taj virus ima visoki afinitet za pločasti epitel i razmnožava se u terminalno diferenciranim epitelnim stanicama. Danas je poznato oko 150 vrsta HPV, od kojih su 40 vrsta uzročnici infekcija u genitalnoj regiji, a samo neki genotipovi imaju maligni potencijal. Zbog mikrotrauma kože i sluznice za vrijeme genitalnog kontakta lakše dolazi do infekcije bazalnog sloja višeslojnog pločastog epitela genitalnog trakta, gdje se virus razmnožava i remeti normalni stanični ciklus. Većina osoba nije svjesna da su nosioci HPV-a i da virus može prenijeti svom spolnom partneru, dakle, najčešće se radi o prolaznoj infekciji. Smatra se da gotovo svaka seksualno aktivna osoba, muškarci i žene, nekad tijekom života dobije HPV infekciju. Imunosni odgovor našeg organizma prepoznaje strane agense i bori se protiv njih, pa 90% HPV infekcija naš organizam svlada u roku dvije godine i osoba nikada nema klinički vidljivih simptoma. No u nekih osoba HPV infekcija može uzrokovati anogenitalne bradavice ili druge promjene. Nema dijagnostičke metode koja može sa sigurnošću ustanoviti koja će osoba razviti klinički vidljive promjene. Posljedice infekcije Najozbiljnija posljedica trajne infekcije onkogenim tipovima humanog papiloma virusa je karcinom vrata maternice kojem prethodi premaligna lezija određenog stupnja (CIN- intraepitelna neoplazija vrata maternice). Osoba najčešće nema nikakvih tegoba dok karcinom nije uznapredovao. Osnovna metoda detektiranja promjena na grlu vrata maternice je redoviti probir PAPA testiranjem (za žene) prema preporukama ginekologa. Karcinom vrata maternice može se razviti godinama i desetljećima nakon HPV infekcije. Iako puno rjeđe, HPV je uzročnik i respiratorne papilomatoze, ali i karcinoma vulve, vagine, penisa i anusa. Simptomi Velik broj oboljelih nema jasnih simptoma bolesti, no danas imamo na raspolaganju dijagnostičke metode uglavnom bazirane na metodama molekularne biologije koje nam omogućavaju brzu i jednostavnu identifikaciju uzročnika, nakon čega slijedi primjereno liječenje. Anogenitalne bradavice se na koži i sluznici anogenitalne regije najčešće pojave nekoliko tjedana ili mjeseci nakon infekcije. Ne uzrokuju nikakve tegobe, osim ovisno o veličini ili lokalizaciji rijetko svrbež ili bol. Dijagnosticiraju se kliničkim pregledom anogenitalne regije (šiljasti ili ravni kondilomi i drugo). Ako se ne liječe, bradavice se mogu povećavati u broju i veličini, ostati iste ili nestati. U 10-20% slučajeva šiljastih kondiloma može se ustanoviti i prisutnost tipa HPV- a visokog rizika, a ravni kondilomi su najčešće uzrokovani tipovima virusa visokog malignog potencijala. Za sada ne postoji specifično protuvirusno liječenje genitalnih infekcija uzrokovanih humanim papiloma virusom, što ujedno znači i povećanu mogućnost ponovne pojave bolesti (recidiv). Recidivi su osobito česti u prva tri mjeseca po završenom liječenju. Koje su metode liječenja? Metode liječenja koje primjenjujemo mogu biti destruktivne metode (ekskohleacija, krioterapija, elektrokauterizacija) kojima prethodi primjena lokalnog anestetika ili primjena imunomodulatornih pripravaka. Odluka koja će metoda biti provedena ovisi o proširenosti bolesti, kliničkoj slici te dogovoru terapeuta i pacijenta. Navedene metode liječenja često se kombiniraju. Postupak liječenja se ponavlja u više navrata, s naglaskom da je primjena destruktivnih metoda često jednokratna i vodi brzoj i učinkovitoj terapiji vidljivih lezija. Liječenjem uklanjamo vidljive promjene na koži i sluznicama, čime nastojimo smanjiti širenje promjena i značajno smanjiti mogućnost infekcije partnera oboljele osobe. Dobra suradnja pacijenta i provođenje terapije prema uputama vodi ka boljem uspjehu liječenja. Osim vidljivih promjena, uz pomoć metode peniskopije, odnosno kolposkopije moguće je ustanoviti prisutnost supkliničke HPV infekcije. Za sada prema dostupnoj literaturi nema jedinstvenih preporuka i stavova za liječenje te faze bolesti. Latentna infekcija pak razumijeva nepostojanje vidljivih promjena na koži i sluznicama, nego prisutnost virusa u tkivu, a dijagnoza se postavlja nakon dokaza prisutnosti HPV DNA u tkivu. Ako žena ima detektiranu HPV infekciju, u 40-60% njenih muških partnera moguće je ustanoviti znakove iste infekcije. Testovi za dijagnostiku HPV infekcije daju nam podatke o zaraženosti genotipovima HPV visokog rizika za razvoj maligne bolesti cerviksa odnosno niskog rizika koji izazivaju anogenitalne bradavice. Jedna osoba često bude zaražena sa više tipova HPV. Prevencija HPV infekcije Prevencija HPV infekcije je odgovorno spolno ponašanje svih dobnih skupina, a osobito adolescenata te program cijepljenja primjenom cjepiva protiv HPV tipa 6,11,16 i 18. Naime, HPV tipa 6 i 11 odgovorni su za 90% slučajeva anogenitalnih bradavica u oba spola, a HPV tipa 16 i 18 za više od 70% slučajeva raka vrata maternice. Cjepivo ima isključivo preventivnu, a ne terapijsku ulogu, dakle nije namijenjeno liječenju. Cijepljenje značajno smanjuje rizik od pojave anogenitalnih bradavica uzrokovanih humanim papilomavirusom u oba spola, displazije vrata maternice i displazijskih lezija na stidnici i rodnici, i najvažnije, smanjuje rizik od pojave raka vrata maternice.