NEW APPROACHES IN HUMAN PAPILLOMAVIRUS (HPV) TREATMENT: ACTIVE HEXOSE-RELATED COMPOUND (AHCC®)

Year 2024, , 714 - 726, 20.05.2024

Zehra Keçeci , Cansu Bölükbaş , Hazal Eken

https://doi.org/10.33483/jfpau.1364203

Abstract

Objective: Human papillomavirus (HPV) poses a serious public health problem as it is the most common sexually transmitted viral infection that can cause warts and cancer on the skin and mucous membranes, depending on its subtypes. Current treatment options only aim to remove warts and improve symptoms, without eradicating the disease. In addition to these treatments, it has been shown that the use of various natural products that support the immune system can be beneficial in the treatment of HPV. Although the pharmacological effects of mushroom extracts on the immune system have not been fully elucidated, they have been used for various health problems in different parts of the world for many years. This review focused on the effects of AHCC®, a mushroom extract, on HPV infection.
Result and Discussion: AHCC®, a standardized, cultured extract of the edible mushroom Lentinula edodes, enriched in acetylated α-1,4-glucans, is among the prominent alternative treatment options in the treatment of HPV due to its pharmacological effects. Preclinical and clinical studies show that AHCC® may be a promising new option for HPV treatment by supporting the immune system.

Keywords

AHCC®, HPV, nutritional supplements

İNSAN PAPİLLOMA VİRÜSÜ (HPV) TEDAVİSİNDE YENİ YAKLAŞIMLAR: AKTİF HEKSOZ İLİŞKİLİ BİLEŞİK (AHCC®)

Abstract

Amaç: İnsan papilloma virüsü (HPV) alt tiplerine bağlı olarak cilt ve mukoza zarlarında siğil ve kanser oluşumuna sebep olabilen cinsel yolla bulaşan en yaygın viral enfeksiyon olması sebebi ile ciddi bir halk sağlığı problemi oluşturmaktadır. Günümüzde HPV tedavisinde hastalığın eradikasyonunu sağlamayan, sadece dışa doğru büyüyen siğillerin uzaklaştırılmasını ve semptomların iyileştirilmesini amaçlayan seçenekler mevcuttur. Bu tedavilerin dışında immün sistemi destekleyici çeşitli doğal ürünlerin kullanımının da HPV tedavisinde faydalı olabileceği gösterilmiştir. Mantar ekstraktlarının bağışıklık sistemi üzerindeki kesin etkileri tam olarak aydınlatılamamış olsa da uzun yıllardan beri dünyanın farklı bölgelerinde çeşitli sağlık sorunları için kullanılmaktadır. Bu derlemede bir mantar ekstratı olan AHCC®’nin HPV enfeksiyonu üzerindeki etkilerine odaklanılmıştır.
Sonuç ve Tartışma: Yenilebilir bir mantar olan Lentinula edodes'in asetillenmiş α-1,4-glukanlar bakımından zenginleştirilmiş, standartlaştırılmış, kültürlenmiş bir özütü olan AHCC® sahip olduğu çeşitli farmakolojik etkileri nedeni ile HPV tedavisinde öne çıkan alternatif tedavi seçenekleri arasında yer almaktadır. Yapılan preklinik ve klinik çalışmalar, AHCC®’nin bağışıklık sistemini destekleyerek HPV tedavisi için umut veren yeni bir seçenek olabileceğini göstermektedir.

Keywords

AHCC®, besin takviyeleri, HPV

References

• 1. Steben, M., Duarte-Franco, E. (2007). Human papillomavirus infection: Epidemiology and pathophysiology. Gynecologic Oncology, 107(2), 2-5. [CrossRef]
• 2. Letafati, A., Sakhavarz, T., Khosravinia, M.M., Ardekani, O.S., Sadeghifar, S., Norouzi, M., Naseri, M., Ghaziasadi, A., Jazayeri, S.M. (2023). Exploring the correlation between progression of human papillomavirus infection towards carcinogenesis and nutrition. Microbial Pathogenesis, 106302. [CrossRef]
• 3. Moens, U. (2018). Human polyomaviruses and papillomaviruses. International Journal of Molecular Sciences, 19(8), 2360. [CrossRef]
• 4. Heidegger, I., Borena, W., Pichler, R. (2015). The role of human papilloma virus in urological malignancies. Anticancer Research, 35(5), 2513-2519.
• 5. Schiffman, M., Doorbar, J., Wentzensen, N., De Sanjosé, S., Fakhry, C., Monk, B.J., Stanley, M.A., Franceschi, S. (2016). Carcinogenic human papillomavirus infection. Nature Reviews Disease Primers, 2(1), 1-20. [CrossRef]
• 6. Sabol, I., Smahelova, J., Klozar, J., Mravak-Stipetic, M., Gheit, T., Tommasino, M., Grce, M., Tachezy, R. (2016). Beta-HPV types in patients with head and neck pathology and in healthy subjects. Journal of Clinical Virology, 82, 159-165. [CrossRef]
• 7. Nicolae, I., Tampa, M., Mitran, C., Ene, C.D., Mitran, M., Matei, C., Musetescu, A., Pituru, S., Pop, C.S., Georgescu, S.R. (2017). Gamma-glutamyl transpeptidase alteration as a biomarker of oxidative stress in patients with human papillomavirus lesions following topical treatment with sinecatechins. Farmacia, 65(4), 617-623.
• 8. Harden, M.E., Munger, K. (2017). Human papillomavirus molecular biology. Mutation Research/Reviews in Mutation Research, 772, 3-12. [CrossRef]
• 9. Dunne, E.F., Park, I.U. (2013). HPV and HPV-associated diseases. Infectious Disease Clinics, 27(4), 765-778. [CrossRef]
• 10. Soheili, M., Keyvani, H., Soheili, M., Nasseri, S. (2021). Human papilloma virus: A review study of epidemiology, carcinogenesis, diagnostic methods, and treatment of all HPV-related cancers. Medical Journal of the Islamic Republic of Iran, 35, 65. [CrossRef]
• 11. Bruni, L., Albero, G., Rowley, J., Alemany, L., Arbyn, M., Giuliano, A.R., Markowitz. L.E., Broutet, N., Taylor, M. (2023). Global and regional estimates of genital human papillomavirus prevalence among men: A systematic review and meta-analysis. The Lancet Global Health, 11(9), e1345-e1362. [CrossRef]
• 12. Akalın, A. (2022). Human papillomavirus (HPV) enfeksiyonu ve HPV aşısında güncel yaklaşımlar. Androloji Bülteni, 24(2), 133-139. [CrossRef]
• 13. Altun, Z., Yarkın, F., Vardar, M.A., Uğuz, A.H. (2011). Çukurova Üniversitesi Tıp Fakültesi Hastanesine başvuran kadınlarda genital human papilomavirus enfeksiyon prevalansı. Türkiye Klinikleri Tıp Bilimleri Dergisi, 31(2), 307-314. [CrossRef]
• 14. Yıldırım, D., Yıldırım, M.E., Bakıcı, M.Z. (2013). Sivas bölgesinde yaşayan kadınlarda servikal örneklerde human papillomavirüs pozitifliği ve genotiplerinin sıklığı. Fırat Tıp Dergisi, 18(2), 94-97.
• 15. Alışkan, H.E., Şanlı, Ö.Ö., Bolat, F.A., Yağınç, D.A., Toprak, U. (2023). Adana ilinde insan papilloma virüs (hpv) genotip prevalansı ve dağılımının belirlenmesi: 2014-2021 yılları arası hastane temelli bir çalışma. Mikrobiyoloji Bülteni. 57. 119-133. [CrossRef]
• 16. Altay‐Kocak, A., Kazanci, F., Dogu‐Tok, C., Onan, A., Erdem, O., Ozkan, S., Bozdayi, G. (2022). The prevalence and distribution of human papillomavirus in 4267 turkish women with or without cervical lesions: A hospital‐based study. Journal of Medical Virology, 94(10), 5026-5032. [CrossRef]
• 17. Onal, M., Katirci, Y., Kocaman, A., Yildiz, C. (2022). Evaluation of cervical smear screening and colposcopy assessments at a tertiary obstetrics and gynecology center in the blacksea region of Turkey: Retrospective chart-review of the last 5 years. Medicine Science, 11(4), 1625-1629. [CrossRef]
• 18. Petca, A., Borislavschi, A., Zvanca, M.E., Petca, R.C., Sandru, F., Dumitrascu, M.C. (2020). Non-sexual HPV transmission and role of vaccination for a better future. Experimental and Therapeutic Medicine, 20(6), 1-1. [CrossRef]
• 19. Avcı, G.A., Bozdayı, G. (2013). Human papillomavirus. Kafkas Journal of Medical Sciences, (3), 136-144. [CrossRef]
• 20. Hirth, J. (2019). Disparities in HPV vaccination rates and HPV prevalence in the United States: A review of the literature. Human Vaccines & İmmunotherapeutics, 15(1), 146-155. [CrossRef]
• 21. Liu, Z., Rashid, T., Nyitray, A.G. (2015). Penises not required: A systematic review of the potential for human papillomavirus horizontal transmission that is non-sexual or does not include penile penetration. Sexual Health, 13(1), 10-21. [CrossRef]
• 22. Wierzbicka, M., San Giorgi, M.R.M, Dikkers, F.G. (2023). Transmission and clearance of human papillomavirus infection in the oral cavity and its role in oropharyngeal carcinoma-A review. Reviews in Medical Virology, 33(1), e2337. [CrossRef]
• 23. Weyandt, G.H., Tollmann, F., Kristen, P., Weissbrich, B. (2011). Low risk of contamination with human papilloma virus during treatment of condylomata acuminata with multilayer argon plasma coaglasyon and CO2 laser ablation. Archives of Dermatological Research, 303(2), 141-144. [CrossRef]
• 24. Ilmarinen, T., Auvinen, E., Hiltunen-Back, E., Ranki, A., Aaltonen, L.M., Pitkäranta, A. (2012). Transmission of human papillomavirus DNA from patient to surgical masks, gloves and oral mucosa of medical personnel during treatment of laryngeal papillomas and genital warts. European Archives of Oto-Rhino-Laryngology, 269(11), 2367-2371. [CrossRef]
• 25. Muñoz, N., Castellsagué, X., de González, A.B., Gissmann, L. (2006). HPV in the etiology of human cancer. Vaccine, 24(3), 1-10. [CrossRef]
• 26. Vinzón, S.E., Rösl, F. (2015). HPV vaccination for prevention of skin cancer. Human Vaccines & İmmunotherapeutics, 11(2), 353-357. [CrossRef]
• 27. Brianti, P., De Flammineis, E., Mercuri, S.R. (2017). Review of HPV-related diseases and cancers. New Microbiol, 40(2), 80-85.
• 28. Markowitz, L.E., Schiller, J.T. (2021). Human papillomavirus vaccines. The Journal of Infectious Diseases, 224(Supplement_4), 367-378. [CrossRef]
• 29. Ocaktan, M.E. (2012). HPV aşıları ve Türkiye açısından bir değerlendirme. Toplum ve Hekim, 27(2), 118-134.
• 30. Castle, P.E., Maza, M. (2016). Prophylactic HPV vaccination: Past, present, and future. Epidemiology & Infection, 144(3), 449-468. [CrossRef]
• 31. Tobian, A.A., Serwadda, D., Quinn, T.C., Kigozi, G., Gravitt, P.E., Laeyendecker. O., Charvat, B., Ssempijja, V., Riedesel, M., Oliver, A.E., Nowak, R.G., Moulton, L.H., Chen M.Z., Reynolds, S.J., Wawer, M.J., Gray, R.H. (2009). Male circumcision for the prevention of HSV-2 and HPV infections and syphilis. New England Journal of Medicine, 360(13), 1298-1309. [CrossRef]
• 32. Backes, D.M., Bleeker, M.C.G., Meijer, C.J.L.M., Hudgens, M.G., Agot, K., Bailey, R.C., Ndinya-Achola, J.O., Hayombe, J., Hogewoning, C.J.A., Moses, S., Snijders, P.J.F., Smith, J.S. (2012). Male circumcision is associated with a lower prevalence of human papillomavirus associated penile lesions among Kenyan men. International Journal of Cancer, 130(8), 1888-1897. [CrossRef]
• 33. Kaderli, R., Schnuriger, B., Brugger, L.E. (2014). The impact of smoking on HPV infection and the development of anogenital warts. International Journal of Colorectal Disease, 29(8), 899–908. [CrossRef]
• 34. Umutoni, V., Schabath, M.B., Nyitray, A.G., Wilkin, T.J., Villa, L.L., Lazcano-Ponce, E., Giuliano, A.R., Sudenga, S.L. (2022). The association between smoking and anal human papillomavirus in the HPV infection in men study. Cancer Epidemiology, Biomarkers & Prevention, 31(8), 1546-1553. [CrossRef]
• 35. Erdoğan, P., Akkaya, F. (2022). Ulusal serviks kanseri tarama programının mevsimsellik ve demografik eğilimleri: COVID-19 pandemisinin etkisi. Turkish Journal of Public Health, 20(1), 152-163. [CrossRef]
• 36. Yaslı, G. (2022). Türkiye’de servikal kanser tarama programı saha değerlendirmesi. Sağlık ve Toplum, 32(3), 14-22.
• 37. Khairkhah, N., Bolhassani, A., Najafipour, R. (2022). Current and future direction in treatment of HPV-related cervical disease. Journal of Molecular Medicine, 100(6), 829-845. [CrossRef]
• 38. Tatti, S., Swinehart, J.M., Thielert, C., Tawfik, H., Mescheder, A., Beutner, K.R. (2008). Sinecatechins, a defined green tea extract, in the treatment of external anogenital warts: A randomized controlled trial. Obstetrics & Gynecology, 111(6), 1371-1379. [CrossRef]
• 39. Gilson, R., Nugent, D., Werner, R.N., Ballesteros, J., Ross, J. (2020). 2019 IUSTI‐Europe guideline for the management of anogenital warts. Journal of the European Academy of Dermatology and Venereology, 34(8), 1644-1653. [CrossRef]
• 40. Ciavattini, A., Tsiroglou, D., Vichi, M., Di Giuseppe, J., Cecchi, S., Tranquilli, A.L. (2012). Topical Imiquimod 5% cream therapy for external anogenital warts in pregnant women: Report of four cases and review of the literature. The Journal of Maternal-Fetal & Neonatal Medicine, 25(7), 873-876. [CrossRef]
• 41. Krogh, G.V., Hellberg, D. (1992). Self-treatment using a 0.5% podophyllotoxin cream of external genital condylomata acuminata in women: A placebo-controlled, double-blind study. Sexually Transmitted Diseases, 19(3), 170-174. [CrossRef]
• 42. Beutner, K.R., Wiley, D.J., Douglas, J.M., Tyring, S.K., Fife, K., Trofatter, K., Stone, K.M. (1999). Genital warts and their treatment. Clinical Infectious Diseases, 28(Supplement_1), 37-56. [CrossRef]
• 43. Theisen, L.L., Erdelmeier, C.A.J., Spoden, G.A., Boukhallouk, F., Sausy, A., Florin, L., Muller, C.P. (2014). Tannins from Hamamelis virginiana bark extract: Characterization and improvement of the antiviral efficacy against influenza A virus and human papillomavirus. PloS One, 9(1), e88062. [CrossRef]
• 44. Choudhari, A.S., Suryavanshi, S.A., Kaul-Ghanekar, R. (2013). The aqueous extract of Ficus religiosa induces cell cycle arrest in human cervical cancer cell lines SiHa (HPV-16 positive) and apoptosis in HeLa (HPV-18 positive). PLoS One, 8(7), e70127. [CrossRef]
• 45. Mahata, S., Pandey, A., Shukla, S., Tyagi, A., Husain, S.A., Das, B.C., Bharti, A.C. (2013). Anticancer activity of Phyllanthus emblica Linn. (Indian gooseberry): Inhibition of transcription factor AP-1 and HPV gene expression in cervical cancer cells. Nutrition and Cancer, 65(sup1), 88-97. [CrossRef]
• 46. Ghasemi, A., Soleimanjahi, H., Razeghi, S., Gorji, A., Tabaraei, A., Moradi, A., Alizadeh, A., Vakili, M.A. (2012). Genistein induces a protective immunomodulatory effect in a mouse model of cervical cancer. Iranian Journal of Immunology, 9(2), 119-127.
• 47. Mahata, S., Maru, S., Shukla, S., Pandey, A., Mugesh, G., Das, B.C., Bharti, A.C. (2012). Anticancer property of Bryophyllum pinnata (Lam.) Oken. leaf on human cervical cancer cells. BMC Complementary and Alternative Medicine, 12(1), 1-11. [CrossRef]
• 48. Li, G.L., Jiang, W., Xia, Q., Chen, S.H., Ge, X.R., Gui, S.Q., Xu, C.J. (2010). HPV E6 down-regulation and apoptosis induction of human cervical cancer cells by a novel lipid-soluble extract (PE) from Pinellia pedatisecta Schott in vitro. Journal of ethnopharmacology, 132(1), 56-64. [CrossRef]
• 49. Yarnell, E. (2015). Herbs against human papillomavirus. Alternative and Complementary Therapies, 21(2), 71-76. [CrossRef]
• 50. Kenner, D. (2001). The Japanese Medicinal Mushroom Immune Enhancer: AHCC®, UT:Woodland Publishing, Pleasant Grove, pp.1-32.
• 51. Ali, H.Z., Mubarak, R. (2012). Active hexose correlated compound improved the gingival integrity of albino rats. Journal of American Science, 8(6), 69-78.
• 52. Fujii, H., Nishioka, N., Simon, R.R., Kaur, R., Lynch, B., Roberts, A. (2011). Genotoxicity and subchronic toxicity evaluation of active hexose correlated compound (AHCC®). Regulatory Toxicology and Pharmacology, 59(2), 237-250. [CrossRef]
• 53. Shin, M.S., Park, H.J., Maeda, T., Nishioka, H., Fujii, H., Kang, I. (2019). The effects of AHCC®, a standardized extract of cultured Lentinura edodes mycelia, on natural killer and T cells in health and disease: Reviews on human and animal studies. Journal Of Immunology Research, 2019, 1-7. [CrossRef]
• 54. Smith, J.A., Gaikwad, A.A., Mathew, L., Rech, B., Faro, J.P., Lucci III, J.A., Bai, Y., Olsen, R.J., Byrd, T.T. (2022). AHCC® supplementation to support immune function to clear persistent human papillomavirus infections. Frontiers in Oncology, 12, 881902. [CrossRef]
• 55. Singh, A., Adam, A., Rodriguez, L., Peng, B.H., Wang, B., Xie, X., Shi, P.Y., Homma, K., Wang, T. (2023). Oral supplementation with AHCC®, a standardized extract of cultured lentinula edodes mycelia, enhances host resistance against SARS-CoV-2 infection. Pathogens, 12(4), 554, 1-13. [CrossRef]
• 56. Daddaoua, A., Martinez-Plata, E., Lopez-Posadas, R., Vieites, J.M., González, M., Requena, P., Zarzuelo, A., Suárez, M.D., Medina F.S., Martinez-Augustin, O. (2007). Active hexose correlated compound acts as a prebiotic and is antiinflammatory in rats with hapten-induced colitis. The Journal of Nutrition, 137(5), 1222-1228. [CrossRef]
• 57. Ritz, B. (2011). Active hexose correlated compound (AHCC®) and immune outcomes in humans: A review. Natural Medicine Journal, 3(1), 3-7.
• 58. Nogusa, S., Gerbino, J., Ritz, B.W. (2009). Low-dose supplementation with active hexose correlated compound improves the immune response to acute influenza infection in C57BL/6 mice. Nutrition Research, 29(2), 139–143. [CrossRef]
• 59. Nishioka, H., Fujii, H., Wakame, K., Sun, B. (2007). Preventive effect of AHCC for avian influenza virus. In 15th International Symposium of the AHCC Research Association, Saporro, Japan.
• 60. Wang, S., Welte, T., Fang, H., Chang, G.J., Born, W.K., O'Brien, R.L., Sun, B., Fujii, H., Kosuna, K., Wang, T. (2009). Oral administration of active hexose correlated compound enhances host resistance to West Nile encephalitis in mice. The Journal of Nutrition, 139(3), 598-602. [CrossRef]
• 61. Ulbricht, C., Brigham, A., Bryan, J.K., Catapang M., Chowdary, D., Costa, D., Culwell, S., D'Auria, D., Giese, N., Iovin, R., Isaac, R., Juturu, V., Liu, A., Mintzer, M., Rusie, E., Shaffer, M., Windsor, R.C. (2013). An evidence-based systematic review of active hexose correlated compound (AHCC) by the natural standard research collaboration. Journal of Dietary Supplements, 10(3), 264-308. [CrossRef]
• 62. Fernández, J., Redondo-Blanco, S., Gutiérrez-del-Río, I., Miguélez, E.M., Villar, C.J., Lombo, F. (2016). Colon microbiota fermentation of dietary prebiotics towards short-chain fatty acids and their roles as anti-inflammatory and antitumour agents: A review. Journal of Functional Foods, 25, 511-522. [CrossRef]
• 63. López-Cauce, B., Urquía, A., Menchén, L., Homma, K., Bolás-Fernández, F., García-Rodriguez, J.J., Puerto, M. (2022). Lentinula edodes extract increases goblet cell number and Muc2 expression in an intestinal inflammatory model of Trichinella spiralis infection. Biomedicine & Pharmacotherapy, 150, 112937. [CrossRef]
• 64. Yanagimoto, H., Satoi, S., Toyokawa, H., Yamamoto, T., Hirooka, S., Yamao, J., Matsui, Y., Kwon, A.H. (2009). P059 the benefıcıal effect of actıve hexose correlated compound (AHCC®), a health food component, in patients with pancreatic or biliary tract cancer who underwent chemotherapy. Clinical Nutrition Supplements, 2(4), 49-50. [CrossRef]
• 65. Sun, B., Wakame, K., Sato, E., Nishioka, H., Aruoma, O.I., Fujii, H. (2009). The effect of active hexose correlated compound in modulating cytosine arabinoside-induced hair loss, and 6-mercaptopurine-and methotrexate-induced liver injury in rodents. Cancer Epidemiology, 33(3-4), 293-299. [CrossRef]
• 66. Hirose, A., Sato, E., Fujii, H., Sun, B., Nishioka, H., Aruoma, O.I. (2007). The influence of active hexose correlated compound (AHCC®) on cisplatin-evoked chemotherapeutic and side effects in tumor-bearing mice. Toxicology and Applied Pharmacology, 222(2), 152-158. [CrossRef]
• 67. Shigama, K., Nakaya, A., Wakame, K., Nishioka, H., Fujii, H. (2009). Alleviating effect of active hexose correlated compound (AHCC®) for anticancer drug-induced side effects in non-tumor-bearing mice. Journal of Experimental Therapeutics & Oncology, 8(1), 43-51.
• 68. Choi, J.Y., Lee, S., Yun, S.M., Suh, D.H., Kim, K., No, J.H., Jeong, E.H., Kim, Y.B. (2018). Active hexose correlated compound (AHCC®) inhibits the proliferation of ovarian cancer cells by suppressing signal transducer and activator of transcription 3 (STAT3) activation. Nutrition and Cancer, 70(1), 109-115. [CrossRef]
• 69. Smith, J.A., Mathew, L., Gaikwad, A., Jaffari, M., Julius, J.M., Julius, J.M., Frumovitz, M., Dalrymple, J.L. (2011). Abstract B79: Evaluation of active hexose correlated compound (AHCC®) for the prevention or delay of tumor growth in human cervical cancer xenograft model. Cancer Prevention Research, 16(3), 300-307. [CrossRef]
• 70. Gao, Y., Zhang, D., Sun, B., Fujii, H., Kosuna, K.I., Yin, Z. (2006). Active hexose correlated compound enhances tumor surveillance through regulating both innate and adaptive immune responses. Cancer Immunology, Immunotherapy, 55, 1258-1266.
• 71. Terakawa, N., Matsui, Y., Satoi, S., Yanagimoto, H., Takahashi, K., Yamamoto, T., Yamao, J., Takai, S., Kwon, A.H., Kamiyama, Y. (2008). Immunological effect of active hexose correlated compound (AHCC) in healthy volunteers: A double-blind, placebo-controlled trial. Nutrition and Cancer, 60(5), 643-651. [CrossRef]
• 72. Smith, J.A., Mathew, L., Gaikwad. A., Rech. B., Burney, M.N., Faro, J.P., Lucci III, J.A., Bai, Y., Olsen, R.J., Byrd, T.T. (2019). From bench to bedside: Evaluation of AHCC supplementation to modulate the host immunity to clear high-risk human papillomavirus infections. Frontiers in Oncology, 9, 173. [CrossRef]