STD Series: Updates on Genital warts

I. Introduction
II. HPV associated Anogenital Cancer
• Increasing incidence of anogenital cancers
• HPV and anogenital cancers
• Common types of HPV causing anogenital cancers
• Risk factors for anogenital cancers
III. Diagnosing HPV and screening for HPV associated cancers
• Detection of HPV
• Screening for cervical cancer
IV. Regimen for Genital Warts
• Current treatment options for genital warts
V. Study of Liquid Nitrogen Cryotherapy as Monotherapy for Condyloma Acuminata (CA)

Genital warts are caused by human papilloma virus (HPV). There are more than hundred types of human papilloma virus and around 40 are estimated to affect the genital area appearing around the vagina, vulva, tip of the penis and the anus. Also known as condylomata acuminata (external genital warts), it is considered one of the common forms of sexually transmitted diseases globally. Warts can vary in its appearance as either flat, cauliflower or resemble raspberries. It can begin as pink or red growths continuing to reach four inches across thus affecting normal sexual intercourse. Majority of the genital warts are normally asymptomatic but based on their location, it can be painful. In most of the cases, it can resolve on its own within a few years but the immunocompromised individuals such as HIV-positive people are the highest burden of HPV and are particularly susceptible to recurrences and treatment failure. Virology HPV is a double-stranded deoxyribonucleic acid virus belonging to the family Papovaviridae. In search of the appropriate cellular host, the virus enters the cutaneous and mucosal epithelium. The mucosa of the genital tract includes the vulva, vagina, cervix, penile shaft, periurethral and perianal regions. The low-risk HPV strains undergo replication separately from the host cell DNA in contrast to the high-risk HPV strains that will incorporate its DNA into the host’s genomic material. This integration of DNA results in the initiation of the E6 and E7 genes stimulating the transcription of oncoproteins. As a result, it will inactivate tumor suppressor genes causing cell proliferation and the risk of malignant progression.

HPV associated Anogenital Cancer

Although the anogenital cancers are generally uncommon, there is a growing incidence currently which is attributed to the increasing HPV transmission. According to CDC report, an average 38,793 HPV-associated cancers are detected every year (23,000 among females and 15,793 among male population) and the most common of these cancers are the cervical carcinomas at 11,771 females. HPV is believed to be responsible for more than 90% of anal and cervical cancers, 70% of vaginal and vulvar cancers and an estimated 60% of penile cancers. The high-risk HPV viral genotypes are 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68, however, the most commonly isolated carcinogenic HPV types are 16 and 18 accounting for 70% of all cervical cancers globally. Most of the risk factors associated with the development of anogenital cancer include receptive anal intercourse, a sexually transmitted disease, genital hygiene, persistent HPV infection, immune deficiency syndrome and cigarette smoking.

Diagnosing HPV and screening for HPV associated cancers

Currently, there are no blood tests or swab to detect HPV and diagnosis is based on visible warts on the genital skin. There are no routine screening tests for HPV related cancers other than cervical cancer. Majority of women presenting abnormal smear have had HPV of the vagina, cervix or the vulva but cervical screening is not a test for an HPV infection. Cervical cancer is usually detected by the routine cervical cancer screening and the HPV DNA test may also be done to detect the type of HPV on the cervix.

Regimen for Genital Warts

The treatment of genital warts poses a therapeutic challenge and is focused on the removal of the lesions rather than elimination of the viral infection. There are several forms of therapeutic options available such as the use of cytotoxic agents, physical ablation and immunomodulation, but no definitive therapy is considered an ideal treatment of genital wart for an overall effectiveness. Most forms of the treatment are uncertain of complete cure achievement with the possibility of recurrence of lesions. Here are some results of the study initiated for the treatment of genital warts; Imiquimod 5% cream – an open-label phase ii pilot study concluded that the preliminary results recommend a 4 week treatment course of five percent imiquimod cream which is effective for the treatment of genital warts. In a comparative study, the efficacy of topical podophyllin and podophyllotoxin were compared as the treatment option among men with genital warts. The study illustrated that 82.8% of men using podophyllin and 89.1% of podophyllotoxin group were completely cured although at the end of a 6 months follow-up, some evidence of recurrence of warts was witnessed. Interferon – It is widely used for its antiproliferative, immunomodulatory and antiviral properties. It is shown to be effective against HPV in vivo, vitro and its ability to destroy extra chromosomal viral DNA from infected cells. Locally-used interferon can be effective by both improving and reducing the recurrence rate. Trochloroacetic acid (TCA) 80-90% solution (Grade B) – It is a destructive acid that burns and erodes the skin which is prepared in 80-90% solutions. Though successful treatment can be attained in a single dose, several applications are usually needed. Surgical intervention – Large genital warts can be surgically removed by excision and in the case of warts present on the cervix, laser or loop electrosurgical excision is required.

Study of Liquid Nitrogen Cryotherapy as Monotherapy for Condyloma Acuminata (CA)

In a need to identify a monotherapy as an effective treatment for CA, a comparative study was conducted. The study consisted of two groups; as monotherapy, one group was subjected to liquid nitrogen cryotherapy while the other group was given liquid nitrogen in combination with podophyllin. The study concluded cryotherapy as a safe and effective treatment of multiple warts and in combination with podophyllin was considered even more effective. Special Considerations During Pregnancy According to CDC, administration of drugs such as Imiquimod, podophyllin and podofilox during pregnancy should be avoided. In some rare cases, HPV types 6 and 11 can result in respiratory papillomatosis among infants but the route of transmission is not entirely known. Also, cesarean should not be conducted with the intention of preventing the transmission of HPV infection to the infants and should only be performed in the case of pelvic obstruction. Prevention measures Gardasil as the vaccine against human papillomavirus was approved by the United States Food and Drug Administration (FDA) in 2006 for children as early as nine years of age. It was used to protect against HPV types 6,11,16 and 18 as the majority of cervical cancers was caused by types 16 and 18 while 6 and 11 were responsible for genital warts in 90% of the cases. In 2014, Gardasil 9 was approved by the FDA to protect against the first generation of Gardasil along with other five HPV strains, 31, 33, 45, 52 and 58. The Advisory Committee for Immunization Practices (ACIP) recommends routine vaccination for women between the ages of 9 to 26 although high efficacy was noted up to the age of 45. The optimal age for men is recommended from age 11 to 12 years although up to age 26 years are also considered optional.

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