In 2016, the World Health Organization estimated that 67% of the global population is infected with herpes simplex virus type 1 (HSV-1), which causes herpes simplex labialis (HSL) [1].The lifetime prevalence of recurrent HSL is 20% to 52.5% [2].It is highly contagious and mainly transmitted through oral-to-oral contact [1]. HSL is a lifelong, often asymptomatic infection that lays dormant in the trigeminal nerve. Common symptoms include prodromal tingling or burning sensation around the mouth and eruption of painful, self-limiting vesicles (“cold sores”) progressing to unsightly crusts [1,2]. HSV-1 recurrence can be triggered by ultraviolet light, stress, premenstrual changes, and surgical procedures; its highly visible nature can lead to embarrassment and psychological distress [2]. Antiviral medications are the standard treatment but have adverse effects such as rash, headache, and gastrointestinal upset [1].

A 2015 Cochrane review [2] assessed the effects of preventative interventions for HSL in immunocompetent people of all ages, analyzing evidence from 32 randomized controlled trials on 19 preventative measures. Primary outcomes and key findings are summarized in Table 1.

Compared to the placebo, long-term oral acyclovir and valaciclovir reduced recurrences, although clinical benefit is limited. Limited data suggest thymopentin, low-level laser therapy (LLLT), and hypnotherapy may be effective, but further research is required. There was no evidence supporting the efficacy of lysine, LongoVital supplementation, gamma globulin, the HSV vaccine, the yellow fever vaccine, levamisole, or interferon. Compared to the placebo, there was no significant increase in adverse effects for any of the interventions assessed.

Further research is needed to establish the safety and efficacy of other preventive methods, such as HSV-1 subunit and dendritic cell–based vaccines, LLLT, and topical corticosteroids [1]. A dendritic cell vaccine pilot study (n=14) reported a 3-fold reduction in recurrence during the posttreatment period [3]. Laser therapy relies on analgesic, anti-inflammatory, anti-infective, and biostimulating effects, promoting tissue regeneration and immune response. Although LLLT is promising, caution is warranted due to heterogenicity in study methods and laser parameters [4].

This Cochrane review [2] confirms the preventative efficacy of long-term oral antivirals, highlights the need for further research on sunscreen and natural sunlight, and emphasizes the importance of defining core outcome sets for future studies to adopt. Establishing additional preventative options for HSL remains of paramount importance, considering its significant disease burden and growing antiviral resistance.