Almost all strains of genital HPV are oncogenic, whether of high potential (e.g., HPV 16, 18, 31, 33, 34) or low potential (e.g., HPV 6, 11), eventually potentially causing invasive disease such as cervical intraepithelial neoplasia, cervical cancers, genital cutaneous and mucosal squamous cell carcinomas (e.g., Bowen's disease) including penile carcinomas. Cervical cancer is the second or third leading cause of cancer deaths in epidemio-logical studies of adult women [1, 3, 5]. Pap smears are cytological sampling of the cervical mucosa and has been able to detect many cases of invasive HPV and has sampling errors, false positives and false negatives
. Viral release from the capsid allows entry of HPV into the DNA of the host, thereby exposing the host to a potentially oncogenic event. Hence, prevention of release of HPV DNA from its capsid is required for complete disease prevention. While abstinence is completely preventive, it is unrealistic as a lifetime prevention strategy. Condoms, as they do not cover the entire genital tract, do not completely prevent the mucosal to mucosal or skin-to-skin contact required for transmission of HPV. Vaccination is therefore the best method for reduction of HPV-related cervical disease in future generations. As HPV 6 and 11 are the most common genital types and 16 and 18 are the most common oncogenic strains, these four strains have been targeted for vaccine development. Unfortunately, there are so many HPV types that complete prevention of genital HPV may require addition of at least another ten strains in the vaccine strategy (e.g., HPV 31, 33, 34).
The first HPV vaccine Phase III trial reported was a monovalent three-dose HPV 16 trial. This trial of 2392 college-aged women (defined as females 16-23 years of age) was the first to demonstrate the capabilities of HPV vaccines. While 3.8 cases of HPV were noted per 100 women treated with placebo, none were noted in vaccinated women. Moreover, 9 cases of cervical intraepithelial neoplasia were noted in placebo and zero with vaccine . Prolonged immunity has been noted with this vaccine .
Bi-valent HPV 16, 18 vaccination (Cerviarix®) was also efficacious in a trial of 1113 women aged 15-25 years. This trial noted 100% efficacy against persistent infection, but only 91.6% efficacy (95% CI 64.5-98.0) against incident infection . In the intention-to-treat analyses, vaccine efficacy was 95.1% (63.5-99.3) against persistent cervical infection with HPV 16/18 and 92.9% (70.0-98.3) against cytological abnormalities associated with HPV 16/18 infection.
Vaccination against HPV is now FDA approved in the United States with the introduction of the quadrivalent three-dose Gardasil®, a vaccine against HPV 6, 11, 16 and 18, approved for prevention in women aged 9-26 years old . The target group for vaccination is young women who may acquire oncogenic strains of HPV through sexual intercourse. Phase II trial of Gardasil in 277 young women (mean age 20.2 years) who received doses at 0, 2 and 6 months demonstrated a 90% fall in combined incidence of persistent infection or disease with vaccine . Injection site reactions and fever were the most common vaccine side effects . However, vaccination was described as ineffective after acquisition of HPV infection, hence vaccination is targeted at women who have not yet had their sexual debut. Vaccination of a single sex is more cost effective and is thought to be adequate for disease reduction, despite not taking advantage of herd immunity . Unfortunately, the vaccine is not approved for males and will not prevent homosexual male HPV transmission. Some authors believe that ideally young males should be added to the vaccination schedule as well .
The vaccines are immunogenic against the VLP whether delivered bronchially or intramuscularly, as Gardasil® . Each HPV sub-type has a unique VLP, which is expressed in the capsid. Vaccine against capsid elements kills the VLP prior to intercalation of HPV DNA into the host genome. VLP vaccines induce a high titer of virion neutralizing antibodies and require little adjuvant.
Vaccination using HPV 6 has been proven ineffective in a clinical trial of HPV type 6L2E7 vaccine in patients with condyloma acuminata. In a controlled trial in which 320 patients with HPV 6 or 11 infection were randomized to receive three doses of vaccine or placebo and additional treatment with podophyllin or ablative therapy, a trend toward better clearance was noted in HPV 6-infected patients, but was not statistically significant. Genital HPV typing showed most patients were infected with multiple HPV types, perhaps accounting for the poor response to monovalent vaccine . Overall vaccine prevention strategies hold great promise at prevention of genital HPV-related morbidity and mortality.
Pulse dye laser destroys the extensive vascular supply required to maintain rapid cellular proliferation in warts. Pulse dye laser can be effective for common and anogenital warts in children . Photodynamic therapy and CO2 laser are two other destructive techniques of wart removal; however, they are painful and can scar [104-106].
There are no anti-HPV medications, but patients with concurrent HIV will have less HPV-related morbidity when treated with anti-retrovirals. Two anti-mitotic chemotherapeutic agents have been described as being helpful in wart therapy. Podophyllin can be used in-office or at home as the extracted podophyllotoxin. 5-Flourouracil in a cream base can be used for common and genital wart therapy . This pyrimidine metabolite interferes with DNA and RNA synthesis. The medication is used locally on a daily basis . Ulceration is a common side effect of 5-flourouracil.
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