“It is better to prevent than to cure”
is one of the best known maxims of the father of clinical medicine Hippocrates
of Kos For more than two millennia physicians have learned
to consider the prevention of any disease a better strategy than treating the
disease. The advent of experimental science and the era of evidence-based
medicine has led to best ever recognition of disease causes and therefore best
ever opportunities of prevention.
Cervical cancer is the third most
frequent cancer worldwide in terms of mortality. It is estimated that
globally up to 2% of women annually develop advanced precancerous neoplasia of
the cervix of CIN stages 2 and 3, cytologically characterized as high-grade
squamous intraepithelial lesions, which if undetected or untreated can lead to
invasive cervical cancer. Almost all such advanced precancerous or
cervical cancer cases are caused by infection with high-risk (for cancer) types
of the human papillomavirus (HPV).
HPV infection is globally the most
common sexually transmitted infection, accounting for approximately 270,000
deaths annually, with 88% of them occurring in developing countries.
Mounting evidence indicates that high-risk HPV types are the etiologic agents
in virtually all cervical cancer cases, in approximately 90% of anal cancers
and in a significant percentage (but less than 50%) of vulvar, penile, oral and
pharyngeal cancers.
Evidence from several studies indicates
that most sexually active adults will be infected at least once with HPV in
their lifetimes, mostly in genital-tract and mouth in which a concordance both
in prevalence rate and HPV type has been noted. HPV infections are known to
be most common in young women and to be related to the number of sexual
partners. Usually these HPV infections appear to be transient, with a
typical clearance period within two years. Nevertheless, there are HPV
infections that do persist over two years and those are the ones that might be
conferring increased risk to women for developing high-grade precancerous
lesions or invasive cervical cancer.
Early detection and treatment of
precancerous lesions can obviously prevent cervical cancer. The Pap-smear test
developed by George Papanicolaou in the 1950s has been utilized in routine
screening programs of many developed countries in order to identify high-grade
cervical intraepithelial neoplasia (CIN2+), treat it and prevent its
progression to invasive cancer. The realization of such national screening programs
has over the years increased the coverage of women taking a Pap-smear test and
as a consequence has reduced the occurrence rate of cervical cancer.
Molecular characterization of tens of
HPV types for more than twenty years has yielded a great amount of data
regarding their neoplastic ability and resulted in their classification as
high-risk and low-risk types. High-risk HPV types 16 and 18, in particular,
appear to be responsible for about 70% of cervical cancer cases and especially
HPV 16 for a large percentage of other cancers. The best prevention
strategy for cervical cancer screening seems to be the combination of HPV
typing with colposcopy, which provides a more sensitive and efficient detection
approach than do methods based solely on cytology.
In recent years, the development of
prophylactic vaccines against the most common HPV types has increased hopes for
prevention of viral infection by immunization of early adolescents before any
sexual activity. Prophylactic vaccination is expected to have a major
impact on the burden of cervical cancer as well as that of other HPV-related
cancers. Despite the fact that the currently available vaccines may
protect against only a few high-risk HPV types (including 16 and 18), several
studies have suggested that vaccination would prevent more than 80% of cervical
cancers worldwide.
