HUMAN PAPILLOMA VIRUS Updates and Vaccination

Dr.T.V.Rao MD

Human Papillomavirus
Human papillomavirus (HPV ) is a member of the
papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in the stratified epithelium of the skin or mucous membranes. While the majority of the nearly 200 known types of HPV cause no symptoms in most people, some types can cause warts (verrucae), while others can in a minority of cases lead to cancers of the cervix, vulva, vagina, and anus in women or cancers of the anus and penis in men.

Nobel Prize for Discoveries

The Nobel Assembly at Karolinska Institutet has awarded the Nobel Prize in Physiology or Medicine 2008 to Harald zur Hausen, Franoise Barr-Sinoussi and Luc Montagnier for their discoveries of two viruses causing severe human diseases.

One half is awarded to Harald zur Hausen "for his

discovery of human papilloma viruses causing cervical cancer" and the other half jointly to
Franoise Barr-Sinoussi and Luc Montagnier "for their discovery of human immunodeficiency virus"

Harald zur Hausen awarded Nobel prize

Sexual Contact mainly spread the Infection

More than 30 to 40 types of HPV are typically transmitted through sexual contact and infect the anogenital region. Some sexually transmitted HPV types may cause genital warts. Persistent infection with "high-risk" HPV typesdifferent from the ones that cause skin wartsmay progress to precancerous lesions and invasive cancer. HPV infection is a cause of nearly all cases of cervical cancer however, most infections with these types do not cause disease.

Immuno suppression and HPV

Immunosuppressed patients experience an increased incidence of warts and cancer of cervix All HPV associated infections occur in HIV / AIDS more frequently

Pathology and Pathogenesis

Transmission occurs by close contact, Viral particles are released from surface of paillomatous lesions Causes infections at cutaneous and mucosal sites.

Clinical Importance Manifestations

Globally more than 660 million people are infected with Genital human papilloma's infections. Most common infection of the Genital tract. 6-2 million new infections occur in USA. Most common in youth < 25 years HPV infections are accepted as the cause of anogenital cancers. Majority ( 99 % ) are linked to HPV type 16 HPV 18 type is found in Cervical carcinomas HPV 16 and 18 are identified in > 70 % of cervical carcinomas He la cells widely used in laboratories are associated with infection with HPV 18 DNA

HPV 16 and 18 are High risk factors

HPV types 6 and 11 are typically labeled as low risk because infection with these types has low oncogenic potential and usually results in the formation of condylomata and low-grade precancerous lesions. HPV types 16 and 18

have emerged as the high-risk types of HPV because they are responsible for most
high-grade intraepithelial lesions that may progress to carcinomas, particularly those in the anogenital and/or mucosal category.

The percentages of cancers caused by oncogenic HPV are as .

Cervical cancer 100% Anal cancer - 90% Vulvar cancer - 40% Vaginal cancer - 40% Oropharyngeal cancer - 12% Oral cancer 3%

The Incidence Differs in Developing World

In many lesser-developed countries, cervical cancer is the most common cancer among women because of the lack of effective screening programs that monitor cervical cytology
by Pap smear. However, a single round of HPV screening has been demonstrated to be far superior to conventional cytology in reducing the incidence of cervical cancer morbidity and mortality.

Can Cause Cancers Several Types of Cancers

HPV infections can persist for many years. Persistent infections with high-risk HPVs are the primary cause of cervical cancer. HPV infections also cause some cancers of the anus, vulva, vagina, penis, and oropharynx

What is the association between HPV infection and cancer?

Persistent HPV infections are now recognized as the cause of essentially all cervical cancers. It was estimated that, in 2010, about 12,000 women in the United States would be diagnosed with this type of cancer and more than 4,000 would die from it. Cervical cancer is diagnosed in nearly half a million women each year worldwide, claiming a
quarter of a million lives annually.

Multiple Sex Partners a Risk Factor

Having many sexual partners is a risk factor for HPV infection. Nevertheless, most HPV infections go away on their own without causing any type of abnormality.
However, even among women who develop abnormal cervical cell changes because of persistent infection with highrisk HPV types, the chances of developing cervical cancer are small, even if the abnormal cells are not treated.

Human Papilloma Virus

Sexually Transmitted Virus which can lead to cervical dysplasia (cancer).

Found in 99.7% of all cervical cancers

Types {16,18,31,45} account for 75% of cervical cancer

Human Papilloma Virus

80% of the sexually active adult population will contract HPV

U.S. spent over $1.6 billion in treating symptoms of HPV

2004 2005
$5-6 billion spent on screening tests such as pap smears.

U.S. estimates 13,000 cases of cervical cancer

More than 5,000 will die from cervical cancer

Sexually Active
We define the sexually active population age range as:

The range in years in which an individual changes sexual partners more than once per year on average

Sexually Active Ages

Given this concept of sexual activity the age ranges for each model are:
HPV 15-30 15 30

20

40

Age (years)

Risk of Transmission
The risk of transmission is based on two factors:

The risk of transmission in one sexual encounter The average number of sexual encounters with one partner

Pathophysiology of HPV Infection

Laboratory research has indicated that HPVs produce proteins known as E5, E6, and E7. These proteins interfere with the cell functions that normally prevent excessive growth. For example, HPV E6 interferes with the human protein p53, which acts to keep tumors from growing. A better understanding of how these proteins interact may help researchers develop ways to interrupt the process by which HPV infection can lead to the growth of abnormal cells

Relative Risk of Transmission

: HPV

Male-to-Female 80% Female-to-Male 70%

How are HPV infections detected?

Cervical cells can be tested to identify high-risk types of HPV that may be present. HPV DNA tests look for viral DNA from multiple high-risk HPV types and can detect the presence of a viral infection before any cell abnormalities become visible. The FDA has approved HPV DNA tests for follow-up testing of women with equivocal cell abnormalities on a Pap test (a screening test to detect cervical cell changes). HPV DNA tests are also approved for general cervical cancer screening of women over the age of 30 when done together with a Pap test. There are currently no approved tests to

detect HPV infections in men.

FDA Approves Vaccine for HPV

The U.S. Food and Drug Administration (FDA) has approved two vaccines to prevent HPV infection: Gardasil and Cervarix. Both vaccines are highly effective in preventing persistent infections with HPV types 16 and 18, two high-risk HPVs that cause most (70 percent) cervical cancers. Gardasil also prevents infection with HPV types 6 and 11, which cause virtually all (90 percent) genital warts . In addition, there is some initial evidence that Cervarix provides partial protection against a few other HPV types that can cause cancer, but further evaluation is required before the magnitude and impact of this effect is understood.

Two Vaccines are Licensed for Human Use

Both Gardasil and Cervarix are based on technology developed in part by National Cancer Institute (NCI) scientists. NCI, a component of the National Institutes of Health, licensed the technology to two pharmaceutical companiesMerck and GSKto develop HPV vaccines for widespread distribution.

Gardasil vaccine
The Gardasil vaccine, which is produced by Merck & Co., Inc. (Merck), is called a quadrivalent vaccine because it protects against four HPV types: 6, 11, 16, and 18. Gardasil is given through a series of three injections into muscle tissue over a 6-month period. The FDA has approved Gardasil for use in females for the prevention of cervical cancer, and some vulvar and vaginal cancers, caused by HPV types 16 and 18 and for use in males and females for the prevention of genital warts caused by HPV types 6 and 11. The vaccine is approved for these uses in females and males ages 9 to 26 .

Cervarix Vaccine
Cervarix is produced by GlaxoSmithKline (GSK). It is called a bivalent vaccine because it targets two HPV types: 16 and 18. This vaccine is also given in three doses over a 6-month period. The FDA has approved Cervarix for use in females ages 10 to 25 for the prevention of cervical cancer caused by HPV types 16 and 18.

The Vaccines are Effective in Targeted HPV types

Gardasil and Cervarix are highly effective in preventing infection with the types of HPV they target. Studies have shown that both Gardasil and Cervarix prevent nearly 100 percent of the precancerous cervical cell changes caused by the types of HPV targeted by the vaccine for up to 4 years after vaccination among women who were not infected at the time of vaccination

HPV is Totally Not Protective ?

Neither of these HPV vaccines has been proven to provide complete protection against persistent infection with other HPV types, although some initial results suggest that both vaccines might provide partial protection against a few additional HPV types that can cause cervical cancer.

Vaccine is Not Totally Protective on all types of HPV

Overall, therefore, about 30 percent of cervical cancers will not be prevented by these vaccines. Also, in the case of Gardasil, 10 percent of genital warts will not be prevented by the vaccine. Neither vaccine prevents other sexually transmitted diseases, and they do not treat HPV infection or cervical cancer.

A Regular Check up for Detection of Cancer Cervix essential even in Immunized

Because the vaccines do not protect against all HPV infections that cause cervical cancer, it is important for vaccinated women to continue to undergo cervical cancer screening as recommended for women who have not been vaccinated.

How long do the vaccines protect against infection?

The duration of immunity is not yet known. Research is being conducted to find out how long protection will last. Phase III clinical trials have shown that Gardasil and Cervarix can provide protection against HPV16 for 4 years. Smaller studies have suggested that protection is likely to last for longer than 4 years, but it is not known if protection conferred through vaccination will be lifelong

Will booster vaccinations be needed?

Studies are under way to determine whether booster vaccinations (supplementary doses of a vaccine, usually smaller than the initial dose or doses, that are given to maintain immunity) are necessary.

Who should get these vaccines?

Both Gardasil and Cervarix are proven to be effective only if given before infection with HPV, so it is recommended that they be given before an individual is sexually active. The FDA's licensing decision includes information about the age and sex for recipients of the vaccine. The FDA approved Gardasil for use in females ages 9 to 26 and approved Cervarix for use in females ages 10 to 25.

Vaccination in Males
Data from Merck show high efficacy of Gardasil in males for preventing genital warts associated with HPV6 and HPV11, the two HPV types that cause most genital warts. The FDA approved Gardasil for use in males ages 9 to 26 to prevent genital warts caused by HPV6 and HPV11.

HPV
Total Sexually Active Population Susceptible Vaccinated

Infectious

Vaccinated Infectious

Recovered

Note: A constant population is maintained. Every year/update in the model a proportion of the population

Enters or ages-in as susceptibles Leaves or ages-out

Concerns on HPV Vaccination

Reports of adverse events after administration of the human papillomavirus (HPV) vaccine (Gardasil, Merck) have been making headlines, and questions over the safety of the vaccine have been raised by consumers, parents, healthcare professionals, and others, notes a recent joint statement from the US Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). But having analyzed the available data, the agencies offer reassurance.

HPV safety is Evaluated

Gardasil is 1 of the "most heavily studied and intensively monitored vaccines," commented John

Iskander, MD, acting director of the Immunization Safety Office at the CDC in Atlanta, Georgia. So far the available
data suggest that it is safe, he said in an interview, although he added that "there are no medical products, including vaccines, that are completely safe and effective."

Adverse-Event Reports on Watchdog Web Sites

The actual reports collected by

VAERS have been made

available on the Web site of the watchdog organization Judicial Watch, which obtained the records from the FDA under the Freedom of Information Act. A compact disc containing 8864 records was sent by the FDA on June 10, 2008.

PAP Smear is Still Important for timely Diagnosis of Caner Cervix

Regardless of whether a woman chooses to be vaccinated or not, the take-home message is to start and continue Pap screening throughout your life," Dr. Harper

Is there a Totally Safe and Highly Effective Vaccine

The question remains unanswered as there is no Vaccine which is totally safe and Highly effective to prevent or cure a Diseases. The facts should be learnt with continuous observation and well communicated Knowledge through various peer reviewed Information

Follow me for more articles of interest on issues on Infectious diseases

Dr.T.V.Rao MD

42

The Programme is Created by Dr.T.V.Rao MD for e Learning resources for Medical and Paramedical Professionals
Email

doctortvrao@gmail.com