Human papilloma virus (HPV) infection is the most widespread infection worldwide among the
sexually active population. Papillomaviruses are a very large and heterogeneous family of
double-stranded DNA viruses (8kb). They have no envelope and have icosahedral symmetry. Their
viral genome is divided into two regions defined as 1) early and 2) late. The early genes
encode the early proteins E1, E2, E4, E5, E6, E7 necessary for viral DNA replication and
cellular transformation. The late genes encode the late proteins L1, L2 which serve for the
formation of the viral capsid. HPV viruses are classified based on their oncogenicity. Those
at low risk are associated with proliferative lesions, generally benign, of the skin and
mucous membranes. The clinical manifestations include common, flat and plantar warts, genital
and flat condylomata acuminata which are the result of sexual transmission of the virus and
which arise on the penis, anus, female genitalia, urethra, perianal area and straight.
High-risk HPVs, on the other hand, are those that integrate into the host's genome and cause
lesions that can evolve into carcinoma over time. However, it has recently been shown that
even viruses normally defined as low risk can cause precancerous lesions in the case of
tumors of the vulva, vagina, penis and anus. In 80% of cases the infection resolves
spontaneously within two years, however in 20% of cases, the infection persists and causes
the onset of lesions of varying degrees which over time can evolve into neck cancer of the
uterus in women or penile cancer in men. In fact, if HPV is now recognized as the etiological
agent of cervical cancer in 99.7% of cases, it is estimated that it is also responsible for
50% of penile tumors and 26-30% of cord tumors oral.
Persistence therefore represents an oncological risk factor for those who contract the
infection, since if the infection persists for over a year, there is a high probability that
the viral DNA integrates into the host's genome. Integration involves the constitutive
expression of some viral oncoproteins (E6/E7) that block the activity of host tumor
suppressor genes (p53/pRB). The blockade of tumor suppressors in turn stimulates an
uncontrolled proliferation of lesions, which, due to a failure to activate the inhibitory
regulatory processes of our organism, leads to tumor development.
In the case of lesions classified as "low grade" (L-SIL), the common practice is to check the
patient after six months, while in the case of lesions classified as "high grade" (H-SIL),
the therapeutic standard is represented by the surgical removal of these lesions. However,
removal of the lesion does not guarantee total eradication of the infection, as the virus
could persist in the adjacent healthy mucosa. Currently, there are no treatments against HPV
infection, nor against the persistence of the virus. Various types of therapies are
associated with primary (vaccination) and secondary (screening programs) prevention programs
for the treatment of clinical manifestations induced by the virus, such as warts. Among the
treatments that are used as normal clinical practice in the field of HPV infections, also for
the treatment of warts, those based on epigallocatechin gallate (EGCG) represent a novelty
that has been proven to be safe and effective.
Epigallocatechin gallate (EGCG), the main polyphenolic component of green tea, has
antioxidant, anti-inflammatory and anticancer properties. Its action has also been
extensively tested on cervical cancer lines, on which EGCG exerts an antiproliferative and
pro-apoptotic action in a dose-dependent manner. A recent study demonstrated that EGCG
increases the expression levels of p53 protein and reduces the levels of viral oncoproteins
E6/E7. A randomized clinical trial has also highlighted how treatment with EGCG has a
chemo-preventive action on the progression of lesions in HPV-positive women with lesions of
various degrees, leading to a reduction in the degree of the lesions themselves.
Considering these elements, the study aims to evaluate the effectiveness of the synergy of
oral Epigallocatechin Gallate as a treatment for Low-grade Cervical Lesions (L-SIL)
associated with Human Papilloma Virus (HPV) infection.