The Bay Area Reporter - January 12, 1996
Rob Sabados, ACT UP/Golden Gate Writers' Pool

HPV is generally transmitted by direct contact or contact with infected objects, but other modes of transmission have been documented. Generally, HPV strains are site-specific; for example, HPV types 16 and 18 primarily affect the genitals while types 13 and 32 affect the mouth. In persons who are immunocompromised, exceptions to this rule are common.

Genital warts, also known as condyloma acuminata, are generally considered to be a sexually transmitted disease (STD). While HPV is sexually transmitted, safer sex precautions offer only limited protection. Male condoms, covering only some or all of the penis, still permit contact between the skin of the groin, genital, and peri-anal areas. Further, HPV is highly resistant to spermicides such as nonoxynol-9.

Like many infections, HPV can reactivate as HIV damages the immune system. One large study of HIV-infected women found that warts begin reappearing at CD4 counts over 500, and become progressively more severe and refractory to treatment as CD4 counts decline. Several large studies, including one done by the Denver Department of Health, have found that as CD4 counts fall, HPV DNA is increasingly incorporated into cellular DNA. The incorporation of HPV DNA into cells is a precursor to both future warts and cancer.

Link to cancer

Warts can progress to more serious conditions, such as cervical and anorectal carcinoma. Upon biopsy, warts frequently show early signs of dysplasia (for example, Bowenoid papulosis). Dysplasia, the medical term for abnormal cell growth, can be viewed as a spectrum, starting with normal cells on one end and dysplasia grades one through three representing increasingly severe abnormalities. Warts represent very mild dysplasia, while some sources believe that grade 3 dysplasia characterizes anal cancer. Dysplasia involving the anus or cervix is sometimes called anal intraepithelial neoplasia (AIN) or cervical intraepithelial neoplasia (CIN), respectively.

In the general population, anal cancer is more common among women than men. Explanations include receptive anal intercourse and migration of HPV from the cervix. Women with a history of cervical dysplasia or cancer are at increased risk for anal dysplasia. In the United States, the anal cancer rates are rising at 2.0% per year among women and 2.3% per year among men. In the San Francisco Bay area, the incidence of anal cancer among single, never-married men increased seven-fold between 1973 and 1989. Other studies have detected as much as a forty-fold increase in incidence.

At present, anal examinations are only performed in response to a specific patient complaint: pain, bleeding, visible warts, etc. No equivalent to the routine gynecological exam, which includes manual examination and cervical cancer screening, exists. Cervical cancer screening, also known as the Pap smear, has reduced the incidence of invasive cervical carcinoma by 80% compared with 1950 levels. By detecting abnormalities early, physicians can effectively treat them, preventing progression to invasive cervical cancer, a condition that frequently carries a grim prognosis.

Many researchers believe that routine screening of men and women who have a history of genital warts, cervical dysplasia or receptive anal intercourse, or who are HIV-positive, would help prevent anal cancer. The cervical pap smear can be easily adapted to anal screening. The physician inserts a moist Dacron swab into the rectum then simultaneously rotates and withdraws it while placing pressure on the anal canal. The swab is then smeared on a slide, fixed (preserved) with alcohol, and sent off for analysis. If abnormalities are found, the physician would insert an anoscope to examine and potentially biopsy any lesions. Warts and dysplasia would then be treated initially and as they recur.

Left untreated, warts will continue to spread, increasing the risk of cancer. For both aesthetic and health reasons, it is important that warts be aggressively treated. Upon visual examination using an anoscope or sigmoidoscope, anal dysplasia is frequently mistaken for anal warts, and treated using the same methods.

Warts are generally treated using methods that are unpleasant and surprisingly low-tech. Common methods include electrocautery (burning off with an electric needle) under local or general anesthesia, topical treatment with caustics such as podophyllin or trichloroacetic acid, freezing with liquid nitrogen, or surgical excision. These procedures can cause localized tissue damage, damage that is particularly slow to heal among people with AIDS.

Limited treatments

Drug treatments are limited at best. Two commonly used drugs are 5-fluorouracil (5-FU, Efudex) and interferon. Interferon-alpha (Intron A, Alferon N) is approved by the Food and Drug Administration (FDA) for treating warts, some Kaposi's sarcoma lesions and other some other conditions. While effective, it is expensive and must be injected directly into the wart, a painful and sometimes awkward task. 5-fluorouracil is a chemotherapy drug which, when used as a topical cream, can help prevent wart recurrence. It is also being studied for treating high-grade cervical dysplasia in women.

By effectively treating warts and HPV infection, it may be possible to prevent progression to dysplasia and cancer. At present, there are several new treatments being developed. These include low-dose systemic interferon and isotretinoin (Accutane), topical HPMPC (cidofovir) cream, and various immunomodulators.

Accutane, a drug approved for acne, has shown clinical benefit in the treatment of anal dysplasia, warts, eosinophilic folliculitis, and KS lesions, either singly or when combined with low doses of interferon. By using relatively low doses of both drugs, researchers were able to minimize side-effects. Unfortunately, investigation into Accutaneís benefits have been slowed by its ability to cause birth defects.

HPMPC is a broad spectrum antiviral drug active against herpes simplex, HPV, CMV, and other viruses. While toxic when used systematically, HPMPC cream may allow for the simultaneous suppression of herpes and warts with minimal toxicity.

Other immunomodulators such as thymostimulin, thymopentin, Immiquimod, DNCB and systemic and local interleukin-2 (IL-2) have shown promising initial results in human and animal studies.

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