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Background: Surgery is the mainstay therapy for HPV-induced laryngeal papillomatosis (LP) and adjuvant therapies are palliative at best. Research revealed that conjugated-linoleic acid (CLA) may improve the outcome of virally-induced diseases. The effects of Clarinol™ G-80 (CLA) and high oleic safflower oil (HOSF) on children with LP (concomitant with surgery) were evaluated., Design: A randomized, double-blinded, crossover and reference-oil controlled trial was conducted at a South African medical university. Study components included clinical, HPV type/load and lymphocyte/cytokine analyses, according to routine laboratory methods., Participants: Overall: ten children enrolled; eight completed the trial; five remained randomized; seven received CLA first; all treatments remained double-blinded., Intervention: Children (4 to 12 years) received 2.5 ml p/d CLA (8 weeks) and 2.5 ml p/d HOSF (8 weeks) with a washout period (6 weeks) in-between. The one-year trial included a post-treatment period (30 weeks) and afterwards was a one-year follow-up period., Main Outcome Measures: Changes in numbers of surgical procedures for improved disease outcome, total/anatomical scores (staging system) for papillomatosis prevention/viral inhibition, and lymphocyte/cytokine counts for immune responses between baselines and each treatment/end of trial were measured., Findings: After each treatment all the children were in remission (no surgical procedures); after the trial two had recurrence (surgical procedures in post-treatment period); after the follow-up period three had recurrence (several surgical procedures) and five recovered (four had no surgical procedures). Effects of CLA (and HOSF to a lesser extent) were restricted to mildly/moderately aggressive papillomatosis. Children with low total scores (seven/less) and reduced infections (three/less laryngeal sub-sites) recovered after the trial. No harmful effects were observed. The number of surgical procedures during the trial (n6/available records) was significantly lower [(p 0.03) (95% CI 1.1; 0)]. Changes in scores between baselines and CLA treatments (n8) were significantly lower: total scores [(p 0.02) (95% CI -30.00; 0.00)]; anatomical scores [(p 0.008) (95% CI -33.00: -2.00)]. Immune enhancement could not be demonstrated., Conclusions: These preliminary case and group findings pave the way for further research on the therapeutic potential of adjuvant CLA in the treatment of HPV-induced LP.

Human papilloma virus-induced recurrent laryngeal papillomatosis is considered a troublesome and dangerous disease, because it can cause airway obstruction. Better understanding of metabolic pathways followed under pathological conditions can contribute to improved therapies by which growth and recurrence may be obviated. Part I of this study presents a clinically relevant total lipid fatty acid profile for papilloma cells, analyzed by gas liquid chromatography and a phosholipid red blood cell profile for RLP patients, analyzed by thin layer chromatography. In the papilloma cells virus interference with delta-6 and delta 5- desaturase activities is prevalent and the n-9 FA metabolic pathway is followed. It is plausible that up-regulated fatty acid synthase and 9 desaturase activities occur, since enhanced saturated fatty acids and monounsaturated fatty acid levels are also prevalent. High saturated fatty acid levels are known for their propensity to interfere with delta-6 and delta-5 desaturase activities and this is reflected in the blood profile of the RLP patients. It is also known that enhanced saturated fatty acid levels can contribute to enhanced cyclooxygenase-2 activity. Furthermore, cumulative oxidative stress with an oxidative burst is responsible for complete exhaustion of exogenous dietary arachidonic acid intake in these patients. The role of linoleic acid needs to be defined. The dietary intakes of lipids and micronutrients in RLP patients and a rationale for adjuvant FA therapy in the management of these patients are discussed in parts II and III of the study.

The course of human papilloma virus (HPV)-induced recurrent laryngeal papillomatosis (RLP) is variable and unpredictable. Some patients experience spontaneous remission, while others suffer from aggressive growth with dire consequences. Unfortunately, HPV DNA can persist in mucosa after treatment and can be reactivated under immunosuppressive conditions. For this reason, these benign tumors are notoriously recurrent. Better understanding of lipid-driven signaling pathways during tumorigenesis and immune responses in RLP patients can contribute to improve therapeutic approaches in an attempt to obviate this disease. Based on a mountain of evidence in the literature that concerns the immunomodulatory potential of certain FAs, it is clear that there is a rationale for adjuvant FA therapy (concurrent application) in the management of RLP. Of particular importance for immune surveillance is that the Th1 pathway in RLP is down-regulated and it is advocated that conjugated linoleic acid (CLA) and eicosapentaenoic acid (EPA) have the ability to restore the Th1/Th2 balance. Therefore, it is proposed that adjuvant FA therapy with CLA and EPA must be included in the therapeutical regime of RLP, since they are considered excellent anti-viral and anti-tumor agents to improve immune conditions and disease outcome. Immunocompetence plays a pivotal role in the clinical course of RLP and, hence, a new direction with adjuvant FA therapy may be the key to prevent recurrence of this disease.

Human papilloma virus (HPV)-induced recurrent laryngeal papillomatosis (RLP) is a chronic debilitating disease often encountered among children of poor socio-economic South African groups. There are a few studies and limited evidence as to what extent nutrition may contribute to this disease. To our knowledge this is the first study that gives an account of dietary FA and micronutrient intakes in RLP patients, according to food frequency questionnaires. The dietary FA profile revealed an excessive linoleic acid (LA) intake syndrome and is also marked by high palmitic acid (PA), oleic acid (OA) and SFA intakes. Research revealed that enhanced LA and PA drive, respectively, mitogenic stimuli and apoptotic resistance during tumorigenesis, whist SFAs are associated with lipid rafts, the Th1 immune response and immunosuppression. Low folate intake, a risk for HPV-infection, and low Zn intake, detrimental for lipid metabolism and immunocompetence, occurred in, respectively, 70% and 20% RLP patients. The poor correlations that were found in RLP patients between essential fatty acids (EFAs) and micronutrients, namely, Mg, Zn and Se, involved in lipid metabolism and immune responses, need proper clarification. Overall, it is plausible that the diet (poor nutrition), a shift in lipid metabolism caused by HPV- infection, environmental smoke and oxidative stress, as well as extra-esophageal acid reflux with secondary inflammation in the larynx are co-factors in the etiology of laryngeal papillomatosis, and that immunocompromised patients are subjected to recurrence. It is imperative to ensure that children with RLP receive proper nutrition and follow a healthy lifestyle to prevent disease recurrence after treatment.