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


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


METHODS
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trials and known specialists in the field were also contacted in an attempt to identify any additional published or unpublished trials.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.


METHODS
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.


METHODS
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.


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).


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.
Glenny
Anne-Marie
AM
Cochrane Oral Health Group, MANDEC, School of Dentistry, University of Manchester, Higher Cambridge Street, Manchester, UK, M15 6FH. a.glenny@manchester.ac.uk
Fernandez Mauleffinch
Luisa M
LM
Pavitt
Sue
S
Walsh
Tanya
T
D000212:Acyclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D006560:Herpes Labialis / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D016867:Immunocompromised Host; D009369:Neoplasms / Q000188:drug therapy*; D011458:Prostaglandins E / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D018139:Simplexvirus; D013283:Stomatitis, Herpetic / Q000188:drug therapy* / Q000517:prevention & control; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000998:Antiviral Agents; D011458:Prostaglandins E; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir