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Topical Cidofovir Effective and Well-tolerated for Anal and Vulva Neoplasia


A topical formulation of the antiviral drug cidofovir (Vistide), best known as a treatment for cytomegalovirus (CMV), also appears effective for short-term treatment of high-grade anal and vulva cancer caused by human papillomavirus (HPV) in people with HIV, according to a report in the October 1, 2012, advance online edition of AIDS.

Even in the era of effective antiretroviral therapy (ART), anal-genital dysplasia (abnormal cell growth) and cancers caused by HPV are more common among people with HIV. HIV positive people are more likely than HIV negative people to carry oncogenic HPV types such as HPV-16 or HPV-18, are less likely to spontaneously clear the virus, and are more likely to progress from mild or low-grade dysplasia to high-grade neoplasia (pre-cancer) and squamous cell carcinoma. Invasive cervical cancer is classified as an AIDS-defining condition, though cancers of the anus, penis, and vulva caused by the same virus are not.

Several treatment options exist for HIV positive people with anal or genital dysplasia, including surgical excision, electrocautery or infrared coagulation (IRC), and topical treatment using imiquimod (Aldara) or 5-fluorouracil (Efudex). But none of these are fully effective, and all have side effects ranging from pain and bleeding to flu-like symptoms.

Elizabeth Stier from Boston University Medical Center, Joel Palefsky from the University of California at San Francisco, and colleagues evaluated the safety and efficacy of topical cidofovir for treatment of high-grade anal and vulvar intraepithelial neoplasia (AIN and VIN, respectively) in people with HIV.

Cidofovir is a nucleotide analog like adefovir (Hepsera, used to treat hepatitis B) and the popular antiretroviral tenofovir (Viread); all were developed by Gilead Sciences. Cidofovir was often used in the early years of the epidemic -- prior to effective ART -- to treat CMV infection of the eye (retinitis), which can lead to blindness. Like other drugs in its class, it is primarily eliminated by the kidneys and can cause kidney toxicity.

This prospective Phase 2a trial, conducted at 8 U.S. clinical sites through the AIDS Malignancy Consortium, enrolled HIV positive individuals with biopsy-proven high-grade AIN lesions of at least 3  cm. The study included 24 men and 9 women; all but 1 of the women had high-grade VIN as well. The average age was 44 years and the mean CD4 T-cell count was approximately 400 cells/mm3. Almost all were on combination ART and the median HIV viral load was < 75 copies/mL.

All participants applied a 1% topical cidofovir cream to AIN and VIN lesions for 6 cycles of 2 weeks; there was no placebo arm. Outcomes were classified as complete response, partial response (> 50% reduction in size), stable disease, or progressive disease.


  • All participants had detectable HPV DNA (most often HPV-16) in pre-treatment specimens.
  • 13 (68%) had at least 1 new HPV type detected post-treatment.
  • 26 participants (79%) completed treatment according to the protocol.
  • 7 people discontinued treatment: 4 lost to follow-up, 2 withdrew due to sid effects, and 1 was excluded after biopsy failed to confirm high-grade AIN.
  • A majority of patients experienced at least partial response in an intent-to-treat analysis:

o   Complete response: 5 people (15%);

o   Partial response: 12 people (36%);

o   Stable disease: 7 people (21%);

o   Progressive disease: 2 people (6%), 1 with invasive cancer and 1 with new areas of high-grade AIN.

  • Treatment was generally well-tolerated.
  • The most common side effects were mild-to-moderate pain, burning, or irritation of treated lesions (25 people) and ulceration (13 people).

"Topical cidofovir had 51% efficacy in the short-term treatment of high-grade [AIN] and VIN with acceptable toxicity in HIV positive individuals," the investigators concluded. "Randomized control studies with more prolonged treatment courses and longer follow-up to assess the durability of the response are needed."

"We report the first prospective, open-label, multi-site study evaluating topical cidofovir for the treatment of high-grade [AIN] and VIN in HIV-infected patients," they elaborated in their discussion. "Our results show that over 65% of participants who completed the therapy had at least a PR, and although local skin reactions were very common, most study participants completed the treatment course."

"Even though complete clearance occurred in only 15%, the partial response in an additional one-third of treated patients is clinically beneficial," they continued. "Many patients with flat low-grade disease may not require treatment and a reduction in high-grade lesion area may enable a targeted and less morbid excision or ablative procedure."

"In the absence of a placebo arm we were not able to distinguish the 'true' response rate from spontaneous regression," they cautioned. "However, prior studies of anal, perianal, and vulvar lesions have shown very low rates of natural regression, especially in the setting of is likely that the rate of spontaneous regression in HIV-infected individuals is low and thus the short-term responses to topical cidofovir are likely not due to natural regression, but due to the study drug."



EA Stier, SE Goldstone, MH Einstein, JM Palefsky, et al. Safetyand efficacy of topical Cidofovir to treat high-grade perianal and vulvar intraepithelial neoplasia in HIV-positive men and women. AIDS. October 1, 2012 (Epub ahead of print).