Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer

Glenny A-M, Fernandez Mauleffinch LM, Pavitt S, Walsh T

Published Online:

January 21, 2009

Treatment of cancer is increasingly effective, but associated with oral complications such as mucositis, fungal infections, bacterial infections and viral infections such as the herpes simplex virus (HSV). Oral complications can impact severely on quality of life and may lead to life-threatening systemic infection. Infection with HSV can cause pain and blistering on or around the lips and within the mouth. Orofacial lesions are most commonly caused by HSV type 1. Aciclovir and other antiviral drugs such as valaciclovir, famiciclovir and penciclovir, have been widely used to treat HSV-related conditions. Recurrent HSV type 1 infection in patients who are immunocompromised due to treatment for cancer may be more aggressive, painful and slower to heal. These more extensive lesions often require much longer treatment and leave the patient more susceptible to developing drug-resistant strains of HSV. This review of 17 trials found evidence that aciclovir is efficacious in the prevention and treatment of HSV infections, in terms of preventing clinical/culture positive HSV infections, reduction in healing time, duration of viral shedding and relief of pain. There is no evidence that valaciclovir is more efficacious than aciclovir, or that a high dose of valaciclovir is better than a low dose of valaciclovir. There is evidence that for prevention, placebo is more efficacious than prostaglandin E. However, in all included trials, risk of bias is unclear. No trials reported on duration of hospital stay, amount of analgesia or patient quality of life.

Abstract (click to read)

Background:

Objectives:

To examine the effects of interventions for the prevention or treatment or both, of herpes simplex virus in patients receiving treatment for cancer.

Search strategy:

We searched the following databases: Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, CANCERLIT, SIGLE and LILACS. The reference list of all related review articles and articles considered to be potentially relevant were checked for further trials. Authors of identified trials and known specialists in the field were also contacted in an attempt to identify any additional published or unpublished trials. Date of most recent search: November 2008.

Selection criteria:

All randomised controlled trials comparing interventions for the prevention or treatment or both of HSV infection in people being treated for cancer. Outcomes were presence/absence of clinical/culture positive HSV infections (prevention), time to complete healing of lesions (treatment), duration of viral shedding, recurrence of lesions, relief of pain, amount of analgesia, duration of hospital stay, cost of oral care, patient quality of life and adverse effects.

Data collection and analysis:

Data were independently extracted, in duplicate, by two review authors. Authors were contacted for details of randomisation, blindness and sample demographics where necessary. Quality assessment was carried out on randomisation, blindness, withdrawals and selective reporting. The Cochrane Collaboration's statistical guidelines were followed and risk ratio (RR) values were calculated using random-effects models.

Main results:

Seventeen trials satisfied the inclusion criteria. Four trials evaluated preventative interventions for HSV lesions, three trials for viral isolates, and eight trials evaluated both outcome measures. A single trial reported on the cost of prophylaxis for HSV. Two trials evaluating treatment reported on time to healing, duration of viral shedding and relief of pain. No trials reported on duration of hospital stay, amount of analgesia or patient quality of life.

In placebo controlled trials, aciclovir was found to be effective for the prevention of HSV infections as measured by oral lesions or viral isolates (RR = 0.16, 95% confidence interval (CI) 0.08 to 0.31 nine trials; RR = 0.17, 95% CI 0.07 to 0.37 nine trials). There is no evidence that valaciclovir is more efficacious than aciclovir, or that higher doses of valaciclovir are more effective than lower doses. Placebo was found to be more effective than prostaglandin E for prevention of viral isolates (RR = 1.87, 95% CI 1.12 to 3.14 one trial).

Aciclovir was also found to be effective for the treatment of HSV in terms of duration of viral shedding (median of 2.5 days versus 17.0 days, P = 0.0002; 2 days compared to more than 9, P = 0.0008), time to first decrease in pain (median 3 days compared to 16, P = 0.04), complete resolution of pain (9.9 days compared to 13.6 days, P = 0.01; median of 6 days compared to 16, P = 0.05), 50% healing (median of 6 days compared to 11, P = 0.01) and total healing (median 13.9 days compared to 20.7 days, P = 0.08; median of 8 days compared to 21, P = 0.0).

Authors' conclusions:

There is evidence that aciclovir is efficacious in the prevention and treatment of herpes simplex virus infections. There is no evidence that valaciclovir is more efficacious than aciclovir, or that a high dose of valaciclovir is better than a low dose of valaciclovir. There is evidence that as a prophylaxis, placebo is more efficacious than prostaglandin E. However, in all included trials, risk of bias is unclear.

This record should be cited as:

Glenny A-M, Fernandez Mauleffinch LM, Pavitt S, Walsh T. Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD006706. DOI: 10.1002/14651858.CD006706.pub2

Assessed as up to date:

November 10, 2008

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Primary Review Group:

Oral Health Group

PEARLS - Practical Evidence About Real Life Situations (click to read)

Clinical question:

How effective are interventions for the prevention and/or treatment of herpes simplex virus (HSV) in patients receiving treatment for cancer?

Bottom line:

Aciclovir is efficacious in the prevention and treatment of HSV infections, in terms of preventing clinical/culture positive HSV infections, reduction in healing time, duration of viral shedding and relief of pain. There is no evidence valaciclovir is more efficacious than aciclovir, or a high dose of valaciclovir is better than a low dose of valaciclovir. There is evidence, for prevention, placebo is more efficacious than prostaglandin E.

Caveat:

No trials reported on duration of hospital stay, amount of analgesia or patient quality of life. In all included trials, risk of bias is unclear.

Context:

Treatment of cancer is increasingly effective, but associated with oral complications, such as mucositis, fungal infections, bacterial infections and viral infections, such as HSV. Oral complications can impact severely on quality of life and may lead to life-threatening systemic infection.

Cochrane Systematic Review:

Glenny A-M et al. Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer. Cochrane Reviews 2009, Issue 1. Article No. CD006706. DOI: 10.1002/14651858.CD006706.pub2. This review contains 17 trials involving 1011 participants.

Authored by:

Brian R McAvoy

Cochrane Primary Health Care Field

Health topics:

Dentistry & oral health > Oral cancer > Oral care for cancer patients

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer

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