HPV prevention and treatment

Primary Prevention (vaccination)

 

Primary prevention against HPV is mainly through vaccination. This is discussed in detail in the section on the HPV vaccine.

 

Primary prevention (prophylaxis) of sexually transmitted infectious diseases has been and still is mainly based on abstaining from sexual intercourse and on the use of physical devices (such as condoms) that reduce the causes of exposure to the infectious agent. Unfortunately, as far as HPV is concerned, condom use seems to reduce the risk of infection transmission, but only partially. This is why the HPV vaccination is currently the best protection from infection.

 

 

Secondary prevention (cervical smear test)

 

Secondary prevention means diagnosing the disease as early as possible, before it manifests clinically.

 

The prevention of neoplasia has been carried out for years through a cytological examination known as the cervical smear test. Since it was introduced in 1955, it has undoubtedly contributed to a drastic (6-7 fold) reduction in the incidence of cervical cancer in Western countries. The cervical smear test consists of collecting (using a spatula and brush) a sample of cervical cells, which die and fall off in the course of the normal process of tissue turnover. The sample is then analysed for abnormal cells under the microscope. 

 

In Italy, cervical screening programmes, which have been implemented or are being implemented in most regions, offer a cervical smear test every three years to women aged between 25 and 64.

 

 The cervical smear test, however, has certain limitations:

•  low sensitivity (30% -87%), resulting in a large component of false negatives;
•  specificity (86%-100%) that is not free of false positives (healthy subjects incorrectly indicated as having a disease).

Screening can now rely on an additional diagnostic weapon: the identification and characterisation of HPV strains that may be present in the genital tract.

This biomolecular diagnostic test has a sensitivity > 90% and a specificity > 99% for the identification of individual HPV strains or HPV groups.

On the other hand, clinical specificity is low, as the presence of HPV is not necessarily associated with disease. Therefore, the two methods (cytological and molecular) are complementary and in certain clinical conditions necessary for the correct diagnostic assessment. Screening is therefore very important for follow-up and early diagnosis.

In addition, further investigations are useful, such as colposcopy, anoscopy and, in the event of tumours affecting the throat, laryngoscopy.

Treatment

 

The treatment of papilloma virus infections is based on treating the outcome, and the decision as to which therapy is most appropriate is also made on the basis that the currently available treatments are not fully effective. It should also be noted that many warts disappear spontaneously. The aim of treatment is to eliminate the lesions rather than to eliminate the virus.

The classic treatments for the various manifestations of the virus have been covered in the papilloma virus disease sheet, which you are encouraged to read for a complete picture of the disease.

 

New treatments

Immunotherapies

Since vaccination will not be widespread for many years and since screening interventions are often expensive and difficult to implement, the development of therapeutic treatments remains urgent.

Understanding the mechanisms of HPV elimination can help develop immunotherapies, which consist of treating a disease by stimulating or suppressing the immune system.

Currently, most of the clinical and animal model research on HPV immunotherapies is understandably focused on the treatment of cervical cancer.

 

Indeed, there are numerous approaches to developing these treatments, such as protein/peptide vaccines, bacterial and viral-based vectors and immunomodulators. One of the most promising examples to date is the therapeutic vaccine VGX-3100, a plasmid containing synthetic versions of the E6 and E7 genes of HPV16 and HPV18, which showed efficacy in a controlled study in improving the regression of high-grade lesions (CIN2/3).

Immunotherapies cannot be expected to treat all acute HPV infections, given their prevalence and often sub-clinical presentations.

However, knowledge about the acute phase could be transferable to fight infections in the chronic phase, e.g. by identifying possible immunostimulants or subtypes of immune cells that help eliminate natural acute infections.

Therefore, insights from the elimination of acute infection may be particularly suitable for the development of therapies against precancerous lesions that are usually removed surgically.

 

Conclusions

State of the fight against the human papilloma virus

Cancers caused by infections differ from other cancers because they can be fought using strategies against infectious diseases through the:

•  identification of risk factors: The identification of risk factors has led to the recognition of closely related oncogenic HPV types as aetiological agents responsible for several cancers.
•   prevention of transmission: Infection can now be prevented through the use of safe and effective vaccines targeting the most oncogenic HPVs together with some non-oncogenic HPVs that cause anogenital warts.
•   early diagnosis in infected individuals: screening programmes for early detection of (pre-)neoplastic lesions caused by HPV infections have also been successful in reducing the burden and prevalence of cervical cancer in high-  income countries. However, their different implementation has also increased inequality between countries.

 

Despite available primary and secondary prevention measures, HPVs will continue to infect millions of people in the near future, causing significant morbidity and mortality worldwide.

Indeed, vaccination coverage varies widely both within and between countries, as does access to screening programmes.

In addition to socio-economic factors, the effectiveness of screening is hampered by the fact that some forms of cancer are more difficult to detect than others. This is the case with glandular forms of cervical cancer as opposed to the more common squamous cell carcinoma.

In addition, HPV-induced cancers at anatomical sites other than the cervix (e.g. anal or oropharyngeal cancers) are increasing in many countries, albeit in different populations.

These cancers are of particular concern, either because they are detected once the carcinogenic process is more advanced, as in the case of neck cancer, or because they affect populations at higher risk, as in the case of anal cancer in HIV MSM (men who have sex with men).

Finally, in economic terms, non-cancerous HPVs should not be neglected since the total health care cost of treating genital warts may exceed that of treating HPV-induced cancers, despite the obvious differences in severity and indirect impact of both diseases.

 

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