Human papillomavirus Totally Explained

Everything about Hpv totally explained

Papillomaviruses are a diverse group of DNA-based viruses that infect the skin and mucous membranes of humans and a variety of animals. Approximately 130 human papillomavirus (HPV) types have been identified.
   Some HPV types can cause warts while others may cause a subclinical infection resulting in precancerous lesions. All HPVs are transmitted by skin-to-skin contact and/or by fomites.
   A group of about 30-40 HPVs is typically transmitted through sexual contact and infect the anogenital region. Some sexually transmitted HPVs may cause genital warts. However, other HPV types which may infect the genitals don't cause any noticeable signs of infection.
   Persistent infection with a "high-risk" subset of sexually transmitted HPVs — different from the ones that cause warts — may lead to potentially precancerous lesions and can progress to invasive cancer. HPV infection is a necessary factor in the development of nearly all cases of cervical cancer.
   A cervical Pap smear is used to detect cellular abnormalities. This allows targeted surgical removal of condylomatous and/or potentially precancerous lesions prior to the development of invasive cervical cancer. Although the widespread use of Pap testing has reduced the incidence and lethality of cervical cancer in developed countries, the disease still kills several hundred thousand women per year worldwide. A recently approved HPV vaccine, Gardasil, that blocks initial infection with four of the most common sexually transmitted HPV types may lead to further decreases in the incidence of HPV-induced cancer.

Prevalence in the United States

Estimates of prevalence vary from 14% to 90%. One reason for the difference is that some studies report women who are currently infected, while other studies report women who have ever been infected.

At a given time

One study found that, during 2003–2004, at any given time, 26.8% of women aged 14 to 59 were infected with at least one type of HPV. This was higher than previous estimates. Of the four types prevented by the Gardasil vaccine, however, only 3.4% were infected, which was lower than previous estimates. Of the high-risk types that cause cancer, 15.2% were infected.
In the year 2000, HPV infection accounted for approximately 6.2 million sexually transmitted diseases among Americans aged 15-44. It is estimated that 74% occurred to people between ages 15-24.

Lifetime

Genital HPV infection is very common, with estimates suggesting that more than 50% of women will become infected with one or more of the sexually transmitted HPV types at some point during adulthood. The American Social Health Association reported estimates that about 75% of sexually active Americans will be infected with HPV at some point in their lifetime.

Information from the CDC

According to the Centers for Disease Control (CDC), by the age of 50 more than 80% of American women will have contracted at least one strain of genital HPV.
Genital HPV is the most common sexual transmitted infection in the United States. About 6.2 million Americans will get infected with genital HPV this year. According to the National Cervical Cancer Coalition (NCCC), 11% of American women don't have regular cervical cancer screenings; women who don't have cervical cancer screenings on a regular basis dramatically increase their chances of developing cervical cancer. About 14,000 women in the United States are diagnosed with cervical cancer disease each year, and more than 3,900 women die in the United States each year from this disease.

Information from the AMA

According to the Journal of the American Medical Association (Dunne, Eileen F. et al, 2007) the prevalence of HPV infection among females in the United States is as follows: Types of warts include:

Common warts: Some "cutaneous" HPV types, such as HPV-1 and HPV-2, cause common skin warts. Common warts are often found on the hands and feet, but can also occur in other areas, such as the elbows or knees. Common warts have a characteristic cauliflower-like surface and are typically slightly raised above the surrounding skin. Cutaneous HPV types don't usually cause genital warts and are not associated with the development of cancer.

Plantar warts are found on the soles of the feet. Plantar warts grow inward, generally causing pain when walking.

Subungual or periungual warts form under the fingernail (subungual), around the fingernail or on the cuticle (periungual). They may be more difficult to treat than warts in other locations.

Flat warts: Flat warts are most commonly found on the arms, face or forehead. Like common warts, flat warts occur most frequently in children and teens. In people with normal immune function, flat warts are not associated with the development of cancer. Genital warts are quite contagious, while common, flat, and plantar warts are much less likely to spread from person to person. All warts can spread from one part of your own body to another.

Genital warts

Genital or anal warts (condylomata acuminata or venereal warts) are the most easily recognized sign of genital HPV infection. Although a wide variety of HPV types can cause genital warts, types 6 and 11 account for about 90% of all cases.
Most people who acquire genital wart-associated HPV types clear the infection rapidly without ever developing warts or any other symptoms. People may transmit the virus to others even if they don't display overt symptoms of infection. However, in the vast majority of cases, this isn't a cause for concern if proper tests are routinely administered.
HPV types that tend to cause genital warts are not the same ones that cause cervical cancer. However, since an individual can be infected with multiple types of HPV, the presence of warts doesn't rule out the possibility of high risk types of the virus also being present.

Cancer

About a dozen HPV types (including types 16, 18, 31 and 45) are called "high-risk" types because they can lead to cervical cancer, as well as anal cancer, vulvar cancer, and penile cancer. Several types of HPV, particularly type 16, have been found to be associated with oropharyngeal squamous-cell carcinoma, a form of head and neck cancer. HPV-induced cancers often have viral sequences integrated into the cellular DNA. Some of the HPV "early" genes, such as E6 and E7, are known to act as oncogenes that promote tumor growth and malignant transformation.
   The p53 protein prevents cell growth in the presence of DNA damage primarily through the BAX domain, which blocks the anti-apoptotic effects of the mitochondrial BCL-2 receptor. In addition, p53 also upregulates the p21 protein, which blocks the formation of the Cyclin D/Cdk4 complex, thereby preventing the phosphorylation of RB and, in turn, halting cell cycle progression by preventing the activation of E2F. In short, p53 is a tumor suppressor gene that arrests the cell cycle when there's DNA damage. The E6 and E7 proteins work by inhibiting tumor suppression genes involved in that pathway: E6 inhibits p53, while E7 inhibits p53, p21, and RB.
   An infection with one or more high-risk HPV types is believed to be a prerequisite for the development of cervical cancer (the vast majority of HPV infections are not high risk); according to the American Cancer Society, women with no history of the virus don't develop this type of cancer. However, most HPV infections are cleared rapidly by the immune system and don't progress to cervical cancer. Because the process of transforming normal cervical cells into cancerous ones is slow, cancer occurs in people who have been infected with HPV for a long time, usually over a decade or more.
   Sexually transmitted HPVs also cause a major fraction of anal cancers and approximately 25% of cancers of the mouth and upper throat (known as the oropharynx) (see figure). The latter commonly present in the tonsil area and HPV is linked to the increase in oral cancers in non-smokers. Engaging in anal sex or oral sex with an HPV-infected partner may increase the risk of developing these types of cancers.

Respiratory papillomatosis

HPV types 6 and 11 can cause a rare condition known as recurrent respiratory papillomatosis, in which warts form on the larynx or other areas of the respiratory tract.

Epidemiology

Cutaneous HPVs

Infection with cutaneous HPVs is ubiquitous. Some HPV types, such as HPV-5, may establish infections that persist for the lifetime of the individual without ever manifesting any clinical symptoms. Like remora suckerfish that hitchhike harmlessly on sharks, these HPV types can be thought of as human commensals. Other cutaneous HPVs, such as HPV types 1 or 2, may cause common warts in some infected individuals. Skin warts are most common in childhood and typically appear and regress spontaneously over the course of weeks to months. About 10% of adults also suffer from recurring skin warts. All HPVs are believed to be capable of establishing long-term "latent" infections in small numbers of stem cells present in the skin. Although these latent infections may never be fully eradicated, immunological control is thought to block the appearance of symptoms such as warts. Immunological control is likely HPV type-specific, meaning that an individual may become immunologically resistant to one HPV type while remaining susceptible to other types.

Genital HPVs

A large increase in the incidence of genital HPV infection occurs at the age when individuals begin to engage in sexual activity (see figure). The great majority of genital HPV infections never cause any overt symptoms and are cleared by the immune system in a matter of months. As with cutaneous HPVs, immunity is believed to be HPV type-specific. A subset of infected individuals may fail to bring genital HPV infection under immunological control. Lingering infection with high-risk HPV types, such as HPVs 16, 18, 31 and 45, can lead to the development of cervical cancer or other types of cancer. In addition to persistent infection with high-risk HPV types, epidemiological and molecular data suggest that co-factors such as the cigarette smoke carcinogen benzo[a]pyrene (BaP) enhance development of certain HPV-induced cancers.
High-risk HPV types 16 and 18 are together responsible for over 65% of cervical cancer cases. penile cancers, anal cancers and head and neck cancers.

Public health and genital HPVs

According to the Centers for Disease Control, "At least 50% of sexually active people will get HPV at some time in their lives."
   The HPV vaccine Gardasil protects against the two strains of HPV that cause 70% of cervical cancer cases, and two strains of HPV that cause 90% of genital warts. The CDC recommends that girls and women between the ages of 11 and 26 be vaccinated.
   Since the Pap test was developed there has been a 70% decrease in cervical cancer deaths over the last 50 years. Pap smear testing has proven to be one of the most successful screening tests in the history of medicine.
   A study published in April 2007 suggests that the act of performing a Pap smear produces an inflammatory cytokine response, which may initiate immunologic clearance of HPV, therefore reducing the risk of cervical cancer. Women who had even a single Pap smear in their history had a lower incidence of cancer. "A statistically significant decline in the HPV positivity rate correlated with the lifetime number of Pap smears received."
   It has been suggested that Pap smear screening for anal cancer might be of benefit for some sub-populations of gay men.

HPV testing

An HPV test detects certain types of human papillomavirus (HPVs), depending on the test. A method for detecting the DNA of high-risk HPVs has recently been added to the range of clinical options for cervical cancer screening. In March 2003, the US FDA approved a "hybrid-capture" test, marketed by Digene, as a primary screening tool for detecting high-risk HPV infections that may lead to cervical cancer. This test was also approved for use as an adjunct to Pap testing, and may be ordered in response to abnormal Pap smear results.
When patients are screened with both HPV testing and Pap testing the sensitivity reaches 100%. HPV testing can diagnose CIN 2-3 among women older than 30 years. The sensitivity of HPV testing alone was 94.6% and specificity was 94.1%. For patients at similar risk to those in this study (0.4% had CIN 2-3), this leads to a positive predictive value of 6.0% and negative predictive value of 100.0% (click here

to adjust these results for patients at higher or lower risk of CIN 2-3).
   In Australia, a self-sampling HPV DNA test - that women can do at home using an ordinary tampon - is being marketed by Tam Pap. It has been approved by the Australian Therapeutic Goods Administration for distribution in Australia.
   According to the CDC there's currently no test commercially available to determine infection in men. Genital warts are the only visible sign of HPV in men, and can be identified with a visual check of the genital area. These visible growths, however, are usually the result of non-carcinogenic HPV types. Vinegar solutions have been used to identify flat warts (with limited success) by making them more distinct, but most providers have found this technique helpful only in moist areas, such as the female genital tract.
   Although it's possible to test for HPV DNA in men, there are no FDA-approved tests for general screening, since the testing is inconclusive and considered medically unnecessary.
   The CDC states on its "STD Facts-HPV Vaccine" page that "An HPV test or a Pap test can tell that a woman may have HPV, but these tests can't tell the specific HPV type(s) that a woman has."

HPV vaccine

On June 8, 2006, the US Food and Drug Administration approved Gardasil, a prophylactic HPV vaccine which is marketed by Merck. The vaccine trial, conducted in adult women with a mean age of 23, showed protection against initial infection with HPV types 16 and 18, which together cause 70% of cervical cancers, and can cause other cancers, such as anal cancer. The vaccine also protects against HPV types 6 and 11, which cause 90 percent of genital warts. Women aged nine through twenty-six can be vaccinated, though the trial didn't test minors. GlaxoSmithKline is expected to seek approval for a prophylactic vaccine targeting HPV types 16 and 18 early in 2007, known as Cervarix. Since the current vaccine won't protect women against all the HPV types that cause cervical cancer, it'll be important for women to continue to seek Pap smear testing, even after receiving the vaccine. Cervical cancer screening recommendations have not changed for females who receive HPV vaccine. Both men and women are carriers of HPV.
   Gardasil vaccine is delivered in a series of three shots over six months at a cost of approximately $360 (US dollars). The CDC recommends that girls and women between the ages of 11 and 26 be vaccinated, Females not yet sexually active can be expected to receive the full benefit of vaccination.
   The vaccine doesn't appear to protect against persistent infection, cervical cancer precursor lesions, or genital warts caused by an HPV type that females are infected with at the time of vaccination. However, females already infected with one or more vaccine HPV types before vaccination would be protected against disease caused by the other vaccine HPV types. Therefore, although overall vaccine effectiveness would be lower when administered to a population of females who are sexually active, and would decrease with older age and likelihood of HPV exposure with increasing number of sex partners, the majority of females in this age group will derive at least partial benefit from vaccination. Women should be advised that results from clinical trials don't indicate the vaccine will have any therapeutic effect on existing HPV infection or cervical lesions.
   HPV vaccine is made up of proteins from the outer coat of the virus (HPV). There is no infectious material in this vaccine. There is also no thimerosal, a mercury based preservative, in the HPV vaccine.
   In November 2007, Merck presented new data on Gardasil. This data indicated that in an investigational study, their HPV vaccine reduced incidence of HPV 6, 11, 16 and 18-related persistent infection and disease in women through age 45. The study evaluated women who were free of infection from at least one vaccine HPV type at the beginning of the study, and who remained free of infection with the relevant HPV type(s) until they completed the three-dose vaccination series. Merck planned to submit this data before the end of 2007 to the U.S. Food and Drug Administration (FDA), and to seek an indication for Gardasil for women through age 45.
   On October 26, 2007, the UK government announced that all girls aged 12 and over in the UK will be vaccinated against HPV for free, in a programme costing £100m. By 2009, this vaccination will become standard NHS practice in the UK.

Smoking avoidance

Carcinogens from tobacco and second-hand smoke are concentrated in the cervix, increasing rate of dysplasia by four to five times, and doubling the risk of cervical cancer.
   According to Marcus Steiner and Willard Cates in the New England Journal of Medicine, "the protection that condoms offer can't be precisely quantified." However, in a study reported in the same issue, of 82 female university students followed for eight months, the incidence of genital HPV infection was 37.8 per 100 patient-years among women whose partners used condoms for all instances of intercourse, compared with 89.3 per 100 patient-years in women whose partners used condoms less than 5% of the time. The researchers concluded that "Among newly sexually active women, consistent condom use by their partners appears to reduce the risk of cervical and vulvovaginal HPV infection."
   Other studies have suggested that regular condom use can effectively limit the ongoing persistence and spread of HPV to additional genital sites in individuals who are already infected.
   Thus, condom use may reduce the risk that infected individuals will progress to cervical cancer or develop additional genital warts. Planned Parenthood recommends condom use to reduce the risk of contracting HPV.

Microbicides

Ongoing research has suggested that several inexpensive chemicals might serve to block HPV transmission if applied to the genitals prior to sexual contact. These candidate agents, known as topical microbicides, are currently undergoing clinical efficacy testing. A recent study indicates that some sexual lubricant brands that use a gelling agent called carrageenan can inhibit papillomavirus infection in vitro. See Carrageenan#Sexual lubricant and microbicide for details.
Clinical trials are needed to determine whether carrageenan-based sexual lubricant gels are effective for blocking the sexual transmission of HPVs in vivo.

Nutrition

Fruits and vegetables

Higher levels of vegetable consumption were associated with a 54% decrease risk of HPV persistence.
However, the study population had low overall serum retinol, suggesting deficiency. A study of serum retinol in a well-nourished population reveals that the bottom 20% had serum retinol close to that of the highest levels in this New Mexico sub-population.

Vitamin C

Risk of type-specific, persistent HPV infection was lower among women reporting intake values of vitamin C in the upper quartile compared with those reporting intake in the lowest quartile.

Vitamin E

HPV clearance time was significantly shorter among women with the highest compared with the lowest serum levels of tocopherols, but significant trends in these associations were limited to infections lasting 120 days) wasn't significantly associated with circulating levels of tocopherols. Results from this investigation support an association of micronutrients with the rapid clearance of incident oncogenic HPV infection of the uterine cervix.
A statistically significantly lower level of alpha-tocopherol was observed in the blood serum of HPV-positive patients with cervical intraepithelial neoplasia. The risk of dysplasia was four times higher for an alpha-tocopherol level < 7.95 mumol/l.

Folic acid

Higher folate status was inversely associated with becoming HPV test-positive. Women with higher folate status were significantly less likely to be repeatedly HPV test-positive and more likely to become test-negative. Studies have shown that lower levels of antioxidants coexisting with low levels of folic acid increases the risk of CIN development. Improving folate status in subjects at risk of getting infected or already infected with high-risk HPV may have a beneficial impact in the prevention of cervical cancer.
However, another study showed no relationship between folate status and cervical dysplasia. A 56% reduction in HPV persistence risk was observed in women with the highest plasma [lycopene] concentrations compared with women with the lowest plasma lycopene concentrations. These data suggests that vegetable consumption and circulating lycopene may be protective against HPV persistence.

CoQ10

Women who had either CIN or cervical cancer had markedly lower levels of CoQ10 in their blood and in their cervical cells than the women who were healthy.

Fish oil

In a 1999 study, Docosahexaenoic acid inhibited growth of HPV16 immortalized cells.

Treatment

"There is currently no cure for HPV infection." Therapies for conditions caused by HPV are addressed in main articles covering the various HPV-related diseases. Relatively new treatment is Imiquimod cream which locally stimulates immune system to attack HPV virus affected areas.

History of discovering link between virus and cancer

The fact that prostitutes have much higher rates of cervical cancer than nuns was a key early observation leading researchers to speculate about a causal link between sexually transmitted HPVs and cervical cancer.

Further Information

Get more info on 'Hpv'.

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