Disease - HPV Human Papilloma

Disease - HPV

HUMAN PAPILLOMA VIRUS: PREVENTION and TREATMENT

Human Papilloma Virus Defined:

Human Papilloma Virus (HPV) includes both non-sexually transmitted and sexually transmitted disease (STD) forms that comprises many individual viruses characterized by the development of non-cancerous wart-like tumors known as papillomas (Taylor, et al. 2005). While initially benign, certain types of HPVs have been identified as high-risk precursors of deadly cancers, especially cervical cancers among women.

Approximately one-third of the more than 100 known types of HPVs are capable of transmission through sexual contact. Many HPV infections never result in detectable symptoms but nevertheless are no known to constitute a serious risk factor in the later development of deadly cervical cancers, highlighting the importance of public education with the aim of prevention (CDC 2006).

Epidemiology:

According to the Centers for Disease Control (CDC), more than three-quarters of all American females contract at least one form of HPV in their lifetime, with approximately 6 million new cases of genital HPVs contracted annually in the U.S.

Statistically, approximately one-quarter of all teenage females and those between the ages of 25 and 50, and nearly one-half of those in their early twenties are infected at any given time, making HPV one of the most common STDs in the U.S. (Dunne, et al. 2007).

Almost 15,000 cases of cervical cancers are diagnosed among women in the U.S.

A of which close to one-third prove fatal. Given the extremely high incidence of HPV infection, the causal relationship between HPV infection and later development of cervical cancer, the deadliness of that disease, and the fact that HPV infection is so often completely asymptomatic, cervical cancer screening is crucially important as a mechanism for diagnosing cervical cancer in its earliest stages.

In addition to cervical cancer in females, HPV is also thought to be related to the development of other forms of cancer in both men and women, including rectal, penile, throat, and oral cancers in both genders. Worldwide, the incidence of cervical cancers is almost half a million cases identified annually, accounting for approximately half as many deaths from the disease. (ACS 2008).

Etiology:

The primary risk factor known to be associated with the transmission of HPV is a high number of sexual partners and failure to use condoms during sexual relations.

While HPVs are a known risk factor in the development of cervical (and other) cancers, most HPV infections resolve spontaneously without medical intervention. However, certain types of HPV present much higher risk of later cancerous tumors because they are associated with abnormal cellular changes in the affected tissues (Garland, et al. 2007).

Other than sexual relations with multiple partners without the protection of condoms, there are no known risk factors specific to the transmission of HPV through sexual contact, except that individuals in overall good health are thought to be more resistant to infection, more generally. Possibly for this reason, women with HPV who smoke and those who have delivered multiple children may be more prone to the cellular abnormalities associated with the subsequent development of cervical cancer than non- smokers and women who have not given birth (Dunne, et al. 2007).

Diagnosis:

The most common test used to diagnose HPV infection is a standard gynecological exam that includes a Pap test. Because HPV infection is so often asymptomatic, the U.S. Surgeon General suggests that all women be tested for HPV infection by the age of 21 or earlier if they are sexually active. The presence of any cellular abnormalities should be further examined directly through the use of colposcope to identify potentially dangerous cell growth within the tissues of the vagina and cervix in conjunction with biopsy of any abnormal tissue removed for testing through the colposcope.

Presently, only women are tested for HPV infection because there is no known method for reliably testing men for HPV. Detailed viral DNA tissue tests are capable of identifying more than one dozen of the high-risk forms of HPV known to be associated with the growth of cervical cancers. While most cases of HPV infection do not produce identifiable symptoms of any kind at the time of infection, certain specific forms may result in vaginal and anal warts (Winer, et al. 2006).

Where HPV infection does result in wart formation, the warts associated with HPV may appear weeks, months, or even years after sexual contact with an individual already infected with HPV. Ironically, the low-risk types of HPV infection are more likely to produce visible vaginal warts alerting the individual to the infection; meanwhile, the high-risk types of HPV infection known to be associated with the later development of cervical cancer produce much more subtle types of warts that are often barely visible by virtue of their smaller size, flatter shape, and the fact that they are more likely to be located deeper within the tissues of the cervix rather than the vagina (Dunne, et al. 2007). The traditional method of classifying abnormal tissues identified in Pap tests is the Dysplasia Scale, according to which cellular abnormalities are classified by relative degree of abnormality into mild, moderate, severe, and precancerous (carcinoma in situ).

Those classifications correspond to more detailed distinctions defined by the Bethesda Pap test (CDC 2006).

According to the Bethesda Pap test reporting and classification system, abnormal tissue samples identified through testing are grouped into specific categories. Atypical Squamous Cells occur in two forms with varying relation to HPV infection; Atypical Glandular Cells located in the cervix or the uterus are not necessarily associated with HPV infection; Adenocarcinoma in Situ (AIS) are precancerous cells located in glandular tissue; Low-Grade Squamous Intraepithelial Lesions (LSIL) are abnormal changes in tissue caused by HPV infection that generally resolve spontaneously; and High-Grade Squamous Intraepithelial Lesions are abnormal cells that do not resolve spontaneously and tend to be much more likely to develop into cancers unless they are treated.

Prognosis:

The vast majority of all HPV infections do not result in long-term medical consequences and resolve spontaneously without ever revealing themselves to the infected individual. However, two specific types of HPV infection are known to be responsible for approximately three-quarters of the 15,000 cases of cervical cancers diagnosed in the U.S. annually, resulting in nearly 5,000 deaths (Markowitz, et al. 2007). For that reason, Pap tests and further cervical tissue screening of suspected HPV infection is strongly recommended as a means of early diagnosis of cervical cancers so that they can be treated before they metastasize and spread to other tissues with deadly results. Failure to treat HPV infection therefore is inconsequential in many cases, but quite dangerous for the unlucky individuals infected by one of the two strains implicated in subsequent cervical cancer growths.

Treatment:

Presently, there is no treatment for HPV infection itself although the symptoms in the forms of warts and other lesions associated with this class of viral infection are treatable through removal by traditional surgical excision, by freezing the tissue with cryosurgery, and through the use of heat in loop electrosurgical excision procedures (LEEP). External genital warts are also treatable through various medications.

The primary value of Pap testing is not to treat the HPV infection itself, but rather, to identify the types of HPV infection known to be associated with later development of cervical cancers for the purpose of follow-up and removal of abnormal or precancerous tissues before they develop into deadly cancers subsequently.

Future Treatments:

Merck developed an HPV preventative vaccine called Gardasil which received Federal Drug Administration (FDA) approval in 2006, pursuant to which the drug company then began lobbying for mandatory vaccination in the same manner as other mandatory childhood vaccinations. Texas became the first state to propose such wide- scale vaccinations but critics point out that Gardasil was actually rushed through the process of FDA approval without extensive clinical trials and that the FDA advisory committee that approved the drug are former Merck employees. Similarly, Merck contributed substantially to political campaigns in Texas, further calling into question potential conflicts of interest (Pharmaceutical News 2008).