The use of curcumin in HPV

Humani papiloma virusi (HPV) uzrokuju češće benigne epitelne lezije, ali i karcinom. Tek dugotrajna infekcija s nekim od visokorizičnih tipova HPV-a dovest će do intraepitelne lezije visokog stupnja i na kraju karcinoma. Onkogeni potencijal HR-HPV oslanja se na ulogu glavnih onkoproteina E6 i E7, koji se vežu pa inaktiviraju ili suprimiraju dva glavna stanična tumor-supresorska gena: p53 i retinoblastoma protein (pRb). Kontinuirana ekspresija ovim onkoproteinima može dovesti do transformacije zaraženih stanica. Oba onkoproteina – E6 i E7 – surađuju u indukciji transformacije epitelnih stanica interakcijom s brojnim staničnim proteinima domaćina, regulatorima stanične aktivnosti.

Let's consider the following facts and data:

• Worldwide, HPV (human papilloma virus) causes 5% of all malignant diseases in men and women.
• HPV is responsible for 100% of cervical cancer, 88% of anal cancer, 70% of vaginal cancer and 43% of pubic cancer.
• Infection with high-risk HPV, together with cellular, immunological, genetic and environmental factors, affects the occurrence and progression of cervical cancer.
• Even after more than 30 years of knowledge that HPV is the cause of cervical cancer, there is still no fully effective treatment for HPV infection.
• Conventional physical removal (destruction/excision) of HPV-induced lesions, such as cryotherapy, phototherapy, LETZ, laser biopsy, localized radiotherapy and knife conization have shown results in the treatment of localized lesions.
• Preventive vaccination with bivalent, quadrivalent and nine-valent vaccines is yielding results, and there are also attempts to develop a therapeutic vaccine.
• Immunomodulators such as interferon and imiquimod are used to stimulate cytokines and improve the immune response to HPV infection.
  Also, antiviral approaches such as RNA interference with nucleotide analogues and natural antioxidants such as polyphenol curcumin (active component of turmeric) and epigallocatechin gallate (active component of green tea) have shown effective therapeutic options against HPV infection.

Unconventional treatment of HPV: what and when to apply?

Potencijal nekonvencionalnih metoda liječenja je u eliminaciji HPV-a u ranim fazama infekcije kada virus nije ugrađen u genom stanice domaćina ili u suzbijanju ekspresije virusnih onkogena koji remete regulacijski ciklus stanica domaćina kao rezultat preobrazbe. Dugotrajna perzistencija određenih tipova HR-HPV, posebno tip 16 i 18 je preduvjet za razvoj intraepitelne neoplazije cerviksa (CIN). Međutim, infekcija HPV-om je najčešće prolazna pojava. Nakon infekcije, virus može perzistirati neko vrijeme što dovodi do razvoja lezije niskog stupnja gdje je virus prisutan u integriranom obliku te se tijekom vremena (15 – 20 godina) razvija u karcinom.

According to the natural history, HPV infections most often show spontaneous clearance (transient infection), however, persistence of high-risk HPV infection for a year or more increases the risk of progression to cancer.On the one hand, low grade lesions (LSIL) should not be treated (ablation/excision) but monitored.

S druge strane, identifikacija HPV-a visokog rizika za progresiju u leziju visokog stupnja (HSIL) je trenutak i mjesto gdje se otvara prostor za liječenje “anti – HPV” terapijskim nekonvencinalnim preparatima, kao što je kurkumin.

Along with already known antioxidant vitamins such as: A, E, C and folic acid, green tea and curcumin also take their place in improving the health of the reproductive organs. Although low-grade lesions usually have homogeneous, genetically stable viral replication, in immunocompromised individuals, therapy focuses on resolving these lesions as early as possible to prevent viral entry, replication, and latency, and thus relapse.

Curcumin and HPV

Curcumin (diferuloylmethane, polyphenol from turmeric powder (lat.Curcuma longa) is a powerful antioxidant that exhibits anti-inflammatory and antitumor properties.
The results of studies from the USA, India, Malaysia, Iran and countries where curcumin has been used since the beginning of Ayurvedic medicine, provide attractive data on the possible use of curcumin in the therapy of tumors caused by HPV as well as the use of its anti-inflammatory and antiviral properties.
Curcumin has been clearly shown to alter the molecular pathways of HPV in cervical cancer cells. So, it can be effective in the prevention and treatment of cervical cancer.

• Analyzing the anti-tumor and antiviral properties of curcumin on cervical cancer cells, in one of the studies, curcumin was shown to be cytotoxic for cancer cells, depending on the concentration, of course.Research has shown how it is cytotoxic activity of curcumin selective for cells infected with HPV16 and HPV18, compared to cells not infected with HPV.
• The balance between tumor cell proliferation and spontaneous cell death via apoptosis, as is known, plays an important role in the regulation of tumor cell growth. Curcumin induces apoptosis in cervical cancer cells. The most characteristic ways of cancer cell apoptosis have also been recorded, namely: nuclear fragmentation and internucleosomal DNA fragmentation.
• Curcumin selectively inhibits the expression of viral oncogenes E6 and E7, which was evident from RT-PCR and Western blotting data, in one of the studies.
• Curcumin reduces (induced increase in BAP) HPV oncoprotein E7 expression. Curcumin blocks IkBα phosphorylation and degradation, which terminates NF kB activation. In this way, curcumin regulates the expression of COX-2, which is regulated by NF kB.

Curcumin has been shown to decrease AP-1 expression and suppress NF-kB transcriptional activation. AP-1 plays a crucial role during the development of cervical cancer because it is through it that HPV achieves binding sites. Curcumin inhibits HPV16 transcription via E6/E7 oncogenes and restores tumor suppressor gene p53, retinoblastoma protein and PTPN13.

Author: Maja Gudelj, MD, specialist in gynecology and obstetrics

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