Human papillomavirus

Human papillomavirus (HPV) is a DNA virus from the papillomavirus family that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes. Most HPV infections are subclinical and will cause no physical symptoms; however, in some people subclinical infections will become clinical and may cause benign papillomas (such as warts [verrucae] or squamous cell papilloma), or cancers of the cervix, vulva, vagina, penis, oropharynx and anus. In particular, HPV16 and HPV18 are known to cause around 70% of cervical cancer cases.

New vaccines have been developed to protect against infection with HPV â€" see HPV vaccines.

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 typesâ€"different from the ones that cause skin wartsâ€"may progress to precancerous lesions and invasive cancer. High-risk HPV infection is a cause of nearly all cases of cervical cancer. However, most infections do not cause disease.

Seventy percent of clinical HPV infections, in young men and women, may regress to subclinical in one year and ninety percent in two years. However, when the subclinical infection persistsâ€"in 5% to 10% of infected womenâ€"there is high risk of developing precancerous lesions of the vulva and cervix, which can progress to invasive cancer. Progression from subclinical to clinical infection may take years; providing opportunities for detection and treatment of pre-cancerous lesions.

In more developed countries, cervical screening using a Papanicolaou (Pap) test or liquid-based cytology is used to detect abnormal cells that may develop into cancer. If abnormal cells are found, women are invited to have a colposcopy. During a colposcopic inspection, biopsies can be taken and abnormal areas can be removed with a simple procedure, typically with a cauterizing loop or, more commonly in the developing worldâ€"by freezing (cryotherapy). Treating abnormal cells in this way can prevent them from developing into cervical cancer. Pap smears have reduced the incidence and fatalities of cervical cancer in the developed world, but even so there were 11,000 cases and 3,900 deaths in the U.S. in 2008. Cervical cancer has substantial mortality worldwide, there are an estimated 490,000 cases and 270,000 deaths each year. There are 48,000 cases of genital warts in UK men each year. HPV causes cancers of the throat, anus and penis as well as causing genital warts.

Signs and symptoms



Over 170 HPV types have been identified and are referred to by number. Types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82 are carcinogenic "high-risk" sexually transmitted HPVs and may lead to the development of cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), penile intraepithelial neoplasia (PIN), and/or anal intraepithelial neoplasia (AIN).

Cancer

In August 2012, the Medscape website released a slides presentation about HPV and cancer risk. The following table shows the incidence of HPV associated cancers in the period of 2004-2008 in the US.

Worldwide in 2002, an estimated 561,200 new cancer cases (5.2% of all new cancers) were attributable to HPV, making HPV one of the most important infectious causes of cancer. 84% of new cervical cancers were in the developing world, compared with about 50% of all new cancers. High-risk oncogenic HPV types (including HPV 16 and HPV 18) are associated with 99.7% of all cervical cancers.

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, vaginal cancer, and penile cancer Several types of HPV, in particular type 16, have been found to be associated with HPV-positive oropharyngeal cancer (OSCC), 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. Oral infection with HPV increased the risk of HPV-positive oropharyngeal cancer independent of tobacco and alcohol use. In the United States, HPV is expected to replace tobacco as the main causative agent for oral cancer.

The p53 protein prevents cell growth and stimulates apoptosis in the presence of DNA damage. The 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 is DNA damage.

E6 has a close relationship with the cellular protein E6-AP (E6-associated protein). E6-AP is involved in the ubiquitin ligase pathway, a system that acts to degrade proteins. E6-AP binds ubiquitin to the p53 protein, thereby flagging it for proteosomal degradation.

Most HPV infections are cleared rapidly by the immune system and do not progress to cervical cancer (see Clearance subsection in Virology). Because the process of transforming normal cervical cells into cancerous ones is slow, cancer occurs in people having been infected with HPV for a long time, usually over a decade or more (persistent infection).

Sexually transmitted HPVs also cause a major fraction of anal cancers and approximately 25% of cancers of the mouth and upper throat (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.

Studies show a link between HPV infection and penile and anal cancer, and the risk for anal cancer is 17 to 31 times higher among gay and bisexual men than among heterosexual men. It has been suggested that anal Pap smear screening for anal cancer might benefit some sub-populations of men or women engaging in anal sex. There is no consensus that such screening is beneficial, or who should get an anal Pap smear.

Further studies have also shown a link between a wide range of HPV types and squamous cell carcinoma of the skin. In vitro studies suggest that the E6 protein of the HPV types implicated may inhibit apoptosis induced by ultraviolet light.

The mutational profile of HPV+ and HPV- head and neck cancer has been reported, further demonstrating that they are fundamentally distinct diseases.

Skin warts

All HPV infections can cause warts (verrucae), which are noncancerous skin growths. Infection with these types of HPV causes a rapid growth of cells on the outer layer of the skin. In a study, HPV types 2, 27 and 57 were most frequently observed with warts, while HPV 1, 2, 63, 27 were commonly observed on clinically normal skin. Types of warts include:

  • Common warts: Some "cutaneous" HPV types 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 can cause genital warts but 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.

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 do not display overt symptoms of infection.

HPV types that tend to cause genital warts are not those that cause cervical cancer. Since an individual can be infected with multiple types of HPV, the presence of warts does not rule out the possibility of high-risk types of the virus also being present.

The types of HPV that cause genital warts are usually different from the types that cause warts on other parts of the body, such as the hands or inner thighs.

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.

These warts can recur frequently, may require repetitive surgery, may interfere with breathing, and in extremely rare cases can progress to cancer.

In the immunocompromised

In very rare cases, HPV may cause epidermodysplasia verruciformis in immunocompromised individuals. The virus, unchecked by the immune system, causes the overproduction of keratin by skin cells, resulting in lesions resembling warts or cutaneous horns.

For instance, Dede Koswara, an Indonesian man developed warts that spread across his body and became root-like growths. Attempted treatment by both Indonesian and American doctors included surgical removal of the warts.

Transmission



Prenatal

Although genital HPV types can be transmitted from mother to child during birth, the appearance of genital HPV-related diseases in newborns is rare. Perinatal transmission of HPV types 6 and 11 can result in the development of juvenile-onset recurrent respiratory papillomatosis (JORRP). JORRP is very rare, with rates of about 2 cases per 100,000 children in the United States. Although JORRP rates are substantially higher if a woman presents with genital warts at the time of giving birth, the risk of JORRP in such cases is still less than 1%.

Genital infections

Since cervical and female genital infection by specific HPV types is highly associated with cervical cancer, those types of HPV infection have received most of the attention from scientific studies.

HPV infections in that area are transmitted primarily via sexual activity.

Of the 120 known human papillomaviruses, 51 species and three subtypes infect the genital mucosa. 15 are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), 3 as probable high-risk (26, 53, and 66), and 12 as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and CP6108).

If a college woman has at least one different partner per year for four years, the probability that she will leave college with an HPV infection is greater than 85%. Condoms do not completely protect from the virus because the areas around the genitals including the inner thigh area are not covered, thus exposing these areas to the infected person’s skin.

Hands

Studies have shown HPV transmission between hands and genitals of the same person and sexual partners. Hernandez tested the genitals and dominant hand of each person in 25 couples every other month for an average of 7 months. She found 2 couples where the man's genitals infected the woman's hand with high risk HPV, 2 where her hand infected his genitals, 1 where her genitals infected his hand, 2 each where he infected his own hand, and she infected her own hand. Hands were not the main source of transmission in these 25 couples, but they were significant.

Partridge reports men's fingertips became positive for high risk HPV at more than half the rate (26% per 2 years) as their genitals (48%). Winer reports 14% of fingertip samples from sexually active women were positive. None of these studies reports whether participants were asked to wash or not wash their hands before testing.

Non-sexual hand contact seems to have little or no role in HPV transmission. Winer found all 14 fingertip samples from virgin women negative at the start of her fingertip study. In a separate report on genital HPV infection, 1% of virgin women (1 of 76) with no sexual contact tested positive for HPV, while 10% of virgin women reporting non-penetrative sexual contact were positive (7 of 72).

Shared objects

Sharing of possibly contaminated objects may transmit HPV. Although possible, transmission by routes other than sexual intercourse is less common for female genital HPV infection. Fingers-genital contact is a possible way of transmission but unlikely to be a significant source.

Blood

Though it has traditionally been assumed that HPV is not transmissible via bloodâ€"as it is thought to only infect cutaneous and mucosal tissuesâ€"recent studies have called this notion into question. Historically, HPV DNA has been detected in the blood of cervical cancer patients. In 2005, a group reported that, in frozen blood samples of 57 sexually naive pediatric patients who had vertical or transfusion-acquired HIV infection, 8 (14.0%) of these samples also tested positive for HPV-16. This seems to indicate that it may be possible for HPV to be transmitted via blood transfusion. However, as non-sexual transmission of HPV by other means is not uncommon, this could not be definitively proven. In 2009, a group tested Australian Red Cross blood samples from 180 healthy male donors for HPV, and subsequently found DNA of one or more strains of the virus in 15 (8.3%) of the samples. However, it is important to note that detecting the presence of HPV DNA in blood is not the same as detecting the virus itself in blood, and whether or not the virus itself can or does reside in blood in infected individuals is still unknown. As such, it remains to be determined whether HPV can or cannot be transmitted via blood. This is of concern, as blood donations are not currently screened for HPV, and at least some organizations such as the American Red Cross and other Red Cross societies do not presently appear to disallow HPV-positive individuals from donating blood.

Virology



HPV infection is limited to the basal cells of stratified epithelium, the only tissue in which they replicate. The virus cannot bind to live tissue; instead, it infects epithelial tissues through micro-abrasions or other epithelial trauma that exposes segments of the basement membrane. The infectious process is slow, taking 12â€"24 hours for initiation of transcription. It is believed that involved antibodies play a major neutralizing role while the virions still reside on the basement membrane and cell surfaces.

HPV lesions are thought to arise from the proliferation of infected basal keratinocytes. Infection typically occurs when basal cells in the host are exposed to infectious virus through a disturbed epithelial barrier as would occur during sexual intercourse or after minor skin abrasions. HPV infections have not been shown to be cytolytic; rather, viral particles are released as a result of degeneration of desquamating cells. The HPV virus can survive for many months and at low temperatures without a host; therefore, an individual with plantar warts can spread the virus by walking barefoot.

HPV is a small DNA virus with a genome of approximately 8000 base pairs. The HPV life cycle strictly follows the differentiation program of the host keratinocyte. It is thought that the HPV virion infects epithelial tissues through micro-abrasions, whereby the virion associates with putative receptors such as alpha integrins and laminins, leading to entry of the virions into basal epithelial cells through clathrin-mediated endocytosis and/or caveolin-mediated endocytosis depending on the type of HPV. At this point, the viral genome is transported to the nucleus by unknown mechanisms and establishes itself at a copy number between 10-200 viral genomes per cell. A sophisticated transcriptional cascade then occurs as the host keratinocyte begins to divide and become increasingly differentiated in the upper layers of the epithelium.

The phylogeny of the various strains of HPV generally reflects the migration patterns of Homo sapiens, and suggests that HPV may have diversified along with the human population. Studies suggest that HPV evolved along five major branches that reflect the ethnicity of human hosts, and diversified along with the human population. Researchers have identified two major variants of HPV16, European (HPV16-E), and Non-European (HPV16-NE).

E6/E7 proteins

The two primary oncoproteins of high risk HPV types are E6 and E7. The “E” designation indicates that these two proteins are expressed early in the HPV life cycle, while the "L" designation indicates late expression. The HPV genome is composed of six early (E1, E2, E4, E5, E6, and E7) ORFs, two late (L1 and L2) ORFs, and a non-coding long control region (LCR). After the host cell is infected viral early promoter is activated and a polycistronic primary RNA containing all six early ORFs is transcribed. This polycistronic RNA then undergoes active RNA splicing to generate multiple isoforms of mRNAs. One of the spliced isoform RNAs, E6*I, serves as an E7 mRNA to translate E7 protein. However, viral early transcription subjects to viral E2 regulation and high E2 levels repress the transcription. HPV genomes integrate into host genome by disruption of E2 ORF, preventing E2 repression on E6 and E7. Thus, viral genome integration into host DNA genome increases E6 and E7 expression to promote cellular proliferation and the chance of malignancy. The degree to which E6 and E7 are expressed is correlated with the type of cervical lesion that can ultimately develop.

Role in cancer

The E6/E7 proteins inactivate two tumor suppressor proteins, p53 (inactivated by E6) and pRb (inactivated by E7). The viral oncogenes E6 and E7 are thought to modify the cell cycle so as to retain the differentiating host keratinocyte in a state that is favourable to the amplification of viral genome replication and consequent late gene expression. E6 in association with host E6-associated protein, which has ubiquitin ligase activity, acts to ubiquitinate p53, leading to its proteosomal degradation. E7 (in oncogenic HPVs) acts as the primary transforming protein. E7 competes for retinoblastoma protein (pRb) binding, freeing the transcription factor E2F to transactivate its targets, thus pushing the cell cycle forward. All HPV can induce transient proliferation, but only strains 16 and 18 can immortalize cell lines in vitro. It has also been shown that HPV 16 and 18 cannot immortalize primary rat cells alone; there needs to be activation of the ras oncogene. In the upper layers of the host epithelium, the late genes L1 and L2 are transcribed/translated and serve as structural proteins that encapsidate the amplified viral genomes. Once the genome is encapsidated, the capsid appears to undergo a redox-dependent assembly/maturation event, which is tied to a natural redox gradient that spans both suprabasal and cornified epithelial tissue layers. This assembly/maturation event stabilizes virions, and increases their specific infectivity. Virions can then be sloughed off in the dead squames of the host epithelium and the viral lifecycle continues. A 2010 study has found that E6 and E7 are involved in beta-catenin nuclear accumulation and activation of Wnt signaling in HPV-induced cancers.

E2 research

Human papillomavirus is a DNA virus that cause skin lesions keratinocytes. There are two categories of HPVs, high and low risk. High-risk papillomaviruses are HPVs-16, 18, 31, 33, 35, 39, 45, 51, 55, 58, and 59, which are often found on cancer cells. HPVs that produce skin lesions are low risk HPVs, but HPV-6 and HPV-11 are associated with genital warts. The mechanism of infection of these viruses has been widely researched, particularly the oncogene protein Papillomaviridae E2/E1 and E6/E7, since they are considered the essential part for the development of cancer cells.

In a recent study, 99.7% of one thousand cases of invasive cervical cancer were HPV positive to HPV16, being the most common followed by HPV-18 DNA. High Risk HPV E6 and E7 are more active than E2 in cellular transformation than low risk HPVs. The oncogenes E7 and E6 have been found to change Keratinocytes by altering their cell cycle. E6 binds to P53 and degrades it preventing cell death apoptosis and promoting the replication of viral DNA. P53 is a repair mechanism that destroys any abnormal cells or arrests the cell cycle. Genetic changes in the DNA, such as, the introduction of viral DNA, which transforms and destabilizes the cell. Additional research has been performed in the apoptotic effects of papillomavirus E2. The research findings that the E2 protein in HeLa cells induce p53, causing arrest of the cell cycle and apoptosis. But, the induce p53 accumulation was not correlated to the cell growth arrest at G1 phase. This suggests that apoptosis and cell cycle arrest are independent of each other. Researchers used biochemical and genetic approaches to test the hypothesis that apoptosis by BPVI and HPV18 E2 proteins in HeLa cells is independent of p53. One experiment demonstrated that E2 induced apoptosis was set off by Bax, one of the best-known p53 promoting genes. Corroborating the independent pathway for cellular apoptosis and cell cycle arrest.

A comparative research study was conducted to study the transcription activity of high and low risk papillomaviruse E2 protein and affinity of the E2 binding regions of high and low risk HPVs. The study used protein encoded in HPV 16, HPV18, and HPV11 and Bovine -1, along with comparative DNA binding shift assays, cell free transcription systems, cofactors, to determine the affinity the oncoprotein E2 of both types of HPVs. The BPV1 has been used to model the replication of papillomaviruse. The viral gene of BPV1 gene contains several promoters that are activated by E2 protein.In vivo studies of DNA using HeLa cells revealed that different types of E2 proteins showed different transcription and repression activities based on the binding sites of E2. In vivo studies also revealed the high transcriptional activity of high risk HPV-16 E2, which suggests that HPV-16 has a very efficient E2 that regulates the E6/E7 oncoproteins that results in the control of the viral life cycle. The less efficient E6/E7 oncoproteins are expressed all lower levels in low risks HPVs. The regulation of the E6 promoter of the high risk E2 protein of the HPVs can lead to the development of cancer due to the viral integration.

Latency period

Once an HPV virion invades a cell, an active infection occurs, and the virus can be transmitted. Several months to years may elapse before squamous intraepithelial lesions (SIL) develop and can be clinically detected. The time from active infection to clinically detectable disease may make it difficult for epidemiologists to establish which partner was the source of infection.

Clearance

Most HPV infections are cleared up by most people without medical action or consequences. The table provides data for high-risk types (i.e. the types found in cancers).

Clearing an infection does not always create immunity if there is a new or continuing source of infection. Hernandez' 2005-6 study of 25 couples reports "A number of instances indicated apparent reinfection [from partner] after viral clearance."

Prevention



HPV infection is the most frequently sexually transmitted disease in the world. Methods of prevention include sexual abstinence, condoms, vaccination and microbicides.

Vaccines

Two vaccines are available to prevent infection by some HPV types: Gardasil, marketed by Merck, and Cervarix, marketed by GlaxoSmithKline. Both protect against initial infection with HPV types 16 and 18, which cause most of the HPV associated cancer cases. Gardasil also protects against HPV types 6 and 11, which cause 90% of genital warts. Gardasil is a recombinant quadrivalent vaccine, whereas Cervarix is bivalent, and is prepared from virus-like particles (VLP) of the L1 capsid protein.

The vaccines provide little benefit to women having already been infected with HPV types 16 and 18. For this reason, the vaccine is recommended primarily for those women not yet having been exposed to HPV during sex. The World Health Organization position paper on HPV vaccination clearly outlines appropriate, cost-effective strategies for using HPV vaccine in public sector programs.

Both vaccines are delivered in three shots over six months. In most countries, they are approved only for female use, but are approved for male use in countries like USA and UK. The vaccine does not have any therapeutic effect on existing HPV infections or cervical lesions. In 2010, 49% of teenage girls in the US got the HPV vaccine, while in comparison around two-thirds of teens received shots for meningitis and DPT vaccine.

Women should continue to seek cervical screening, such as Pap smear testing, even after receiving the vaccine. Cervical cancer screening recommendations have not changed for females who receive HPV vaccine. Without continued screening, the number of cervical cancers preventable by vaccination alone is less than the number of cervical cancers prevented by regular screening alone.

Both men and women are carriers of HPV. The Gardasil vaccine also protects men against anal cancers and warts and genital warts.

No efficacy trials for children under 15 have been performed. Duration of vaccine efficacy is not yet answered by rigorous methodologic trials. Cervarix efficacy is proven for 7.4 years with published data through 6.4 years while Gardasil efficacy is proven for 5 years. Age of vaccination is less important than the duration of efficacy.

Condoms

The Centers for Disease Control and Prevention says that male "condom use may reduce the risk for genital human papillomavirus (HPV) infection" but provides a lesser degree of protection compared with other sexual transmitted diseases "because HPV also may be transmitted by exposure to areas (e.g., infected skin or mucosal surfaces) that are not covered or protected by the condom."

Female condoms provide somewhat greater protection than male condoms, as the female condom allows for less skin contact.

Studies have suggested that regular condom use can effectively limit the ongoing persistence and spread of HPV to additional genital sites in individuals already infected.

Microbicides

See also main articles: Microbicides, Microbicides for sexually transmitted diseases

A 2005 review article 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 2006 in vitro study and a 2007 mouse study suggested that some sexual lubricant brands that use a gelling agent called carrageenan may prevent papillomavirus infection. A 2010 International Papillomavirus Conference poster presentation announced that a substudy of a South African HIV-prevention clinical trial found a lower prevalence of high risk HPV infection in users of a carrageenan-based vaginal microbicide, Carraguard, developed by the Population Council, versus placebo users at the end of the trial (prevalence of high risk HPV infection at the beginning of the trial was not ascertained).

Oral infection

A review of scientific studies in healthy subjects has found carcinogenic HPV in 3.5% of the study's subjects and HPV16 in 1.3%. Men have higher prevalence of oral HPV than women.

Oral HPV infection is associated with HPV-positive oropharyngeal cancer. Odds of oral HPV infection increases with the number of recent oral sex partners or open-mouthed kissing partners. Nonsexual oral infection through salivary or cross transmission is also plausible.

Diagnosis



There are multiple types of HPV, sometimes called "low risk" and "high risk" types. Low risk types cause warts and high risk types can cause lesions or cancer.

Health guidelines recommend HPV testing in patients with specific indications including certain abnormal Pap test results. Patients with high risk HPV may need more frequent and aggressive examination including colposcopy or biopsy. Patients with low risk HPV, however, have no indication for HPV testing. This is because the identification of low-risk HPV is not treated, and therefore test results would not change a patient's care.

Cervical testing

According to the National Cancer Institute, “The most common test detects DNA from several high-risk HPV types, but it cannot identify the type(s) that are present. Another test is specific for DNA from HPV types 16 and 18, the two types that cause most HPV-associated cancers. A third test can detect DNA from several high-risk HPV types and can indicate whether HPV-16 or HPV-18 is present. A fourth test detects RNA from the most common high-risk HPV types. These tests can detect HPV infections before cell abnormalities are evident.

“Theoretically, the HPV DNA and RNA tests could be used to identify HPV infections in cells taken from any part of the body. However, the tests are approved by the FDA for only two indications: for follow-up testing of women who seem to have abnormal Pap test results and for cervical cancer screening in combination with a Pap test among women over age 30.”

In April 2011, the Food and Drug Administration approved the cobas HPV Test, manufactured by Roche.” This cervical cancer screening test “specifically identifies types HPV 16 and HPV 18 while concurrently detecting the rest of the high risk types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68).”

The cobas HPV Test was evaluated in the ATHENA trial, which studied more than 47,000 U.S. women 21 years old and older undergoing routine cervical cancer screening. Results from the ATHENA trial demonstrated that 1 in 10 women, age 30 and older, who tested positive for HPV 16 and/or 18, actually had cervical pre-cancer even though they showed normal results with the Pap test.

In March 2003, the U.S. Food and Drug Administration (FDA) approved the Hybrid Capture 2 test manufactured by Qiagen/Digene, which is a "hybrid-capture" test as an adjunct to Pap testing. The test may be performed during a routine Pap smear. It detects the DNA of 13 "high-risk" HPV types that most commonly affect the cervix, it does not determine the specific HPV types. Hybrid Capture 2 is the most widely studied commercially available HPV assay and the majority of the evidence for HPV primary testing in population based screening programmes is based on the Hybrid Capture 2 assay.

The recent outcomes in the identification of molecular pathways involved in cervical cancer provide helpful information about novel bio- or oncogenic markers that allow monitoring of these essential molecular events in cytological smears, histological, or cytological specimens. These bio- or onco- markers are likely to improve the detection of lesions that have a high risk of progression in both primary screening and triage settings. E6 and E7 mRNA detection PreTect HPV-Proofer, (HPV OncoTect) or p16 cell-cycle protein levels are examples of these new molecular markers. According to published results, these markers, which are highly sensitive and specific, allow to identify cells going through malignant transformation.

In October 2011 the US Food and Drug Administration approved the Aptima HPV Assay test for RNA created when and if any HPV strains start creating cancers (see virology).

The vulva/vagina has been sampled with Dacron swabs and shows more HPV than the cervix. Among women who were HPV positive in either place, 90% were positive in the vulvovaginal region, 46% in the cervix.

Oral testing

In February 2010 Quest Diagnostics released OraRisk, a test to identify which HPV types are present in saliva.

Saliva was positive for HPV in Iran in 41% of 22 patients with oral squamous cell carcinoma, and in 25% of 20 people without cancer. Studies have found heightened HPV in mouth cell samples from people with oral squamous cell carcinoma. Studies have not found significant HPV in mouth cells after sampling with toothbrushes (5 of 2,619 samples) and cytobrushes (no oral transmission found).

Testing men

Research studies have tested for and found HPV, including high-risk types (i.e. the types found in cancers), on fingers, mouth, saliva, anus, urethra, urine, semen, blood, scrotum and penis. However, most research tests have used Dacron swabs and custom analysis not available to the general public.

A Brazilian study used the readily available Qiagen/Digene test mentioned above (off label) to test men's penis, scrotum and anus. Each of the 50 men had been a partner for at least 6 months of a woman who was positive for high risk HPV. They found high risk HPV on 60% of these men, primarily the penis. "The specimens were obtained using a vigorous motion of the conical brush included in the Digene kit" "after spraying the anogenital region with saline solution."

A slightly different method also used cytobrushes (but custom lab analysis) and found 37% of 582 Mexican army recruits positive for high risk HPV. They were told not to wash genitals for 12 hours before sampling. (Other studies are silent on washing, a particular gap in studies of hands). They included the urethra as well as scrotum and penis, but the urethra added less than 1% to the HPV rate. Studies like this led Giuliano to recommend sampling the glans, shaft and crease between them and scrotum, since sampling the urethra or anus added very little to diagnosis. Dunne recommends glans, shaft, their crease, and foreskin.

A small study of cytobrushes on 10 US men where the brush was wet, rather than the skin, found 2 of 10 men were positive for HPV (type not reported). Their lab analysis was not the same as either study above. This small study found 4 of 10 men positive for HPV when skin was rubbed with 600 grit emery paper, then swabbed with a wet Dacron swab. Since emery paper and brush were analyzed together at the lab, it is not known if the emery paper collected viruses or loosened them for the swab to collect.

Studies have found collection by men from their own skin (with emery paper and Dacron swabs) as effective as by a clinician, sometimes more so, since patients were more willing to scrape vigorously.

Other studies have used similar cytobrushes to sample fingertips and under the fingernails, though without wetting the area or brush.

Other studies analyzed urine, semen and blood and found varying amounts of HPV, but there is no publicly available test for them.

There is not a wide range of tests even though HPV is common. Clinicians depend on the vaccine among young people and high clearance rates (see Clearance subsection in Virology) to create a low risk of disease and mortality, and treat the cancers when they appear. Others believe that reducing HPV infection in more men and women, even when it has no symptoms, is important (herd immunity) to prevent more cancers rather than just treating them. Where tests are used, negative test results show safety from transmission, and positive test results show where shielding (condoms, gloves) is needed to prevent transmission until the infection clears.

Other testing

Although it is possible to test for HPV DNA in other kinds of infections, there are no FDA-approved tests for general screening in the United States or tests approved by the Canadian government, since the testing is inconclusive and considered medically unnecessary.

Genital warts are the only visible sign of low-risk genital HPV, and can be identified with a visual check. These visible growths, however, are the result of non-carcinogenic HPV types. Five percent acetic acid (vinegar) is used to identify both warts and squamous intraepithelial neoplasia (SIL) lesions with limited success by causing abnormal tissue to appear white, but most doctors have found this technique helpful only in moist areas, such as the female genital tract. At this time, HPV test for males are used only in research.

Research into testing for HPV by antibody presence has been done. The approach is looking for an immune response in blood, which would contain antibodies for HPV if the patient is HPV positive. The reliability of such tests hasn't been proven, as there hasn't been a FDA approved product as of March 2014; testing by blood would be a less invasive test for screening purposes.

Treatment



There is currently no specific treatment for HPV infection. However, the viral infection, more often than not, clears to undetectable levels by itself. According to the Centers for Disease Control and Prevention, the body’s immune system clears HPV naturally within two years for 90% of cases (see Clearance subsection in Virology for more detail). However, experts do not agree on whether the virus is completely eliminated or reduced to undetectable levels, and it is difficult to know when it is contagious.

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. 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 HPV type-specific, meaning that an individual may become resistant to one HPV type while remaining susceptible to other types.

Lung cancer

There has been evidence linking HPV to benign and malignant tumors of the upper respiratory tract. The International Agency for Research on Cancer (IARC) have found that people with lung cancer were significantly more likely to have several high-risk forms of HPV antibodies compared to those who did not have lung cancer. Researchers looking for HPV among 1,633 lung cancer patients and 2,729 people without the lung disease found that people with lung cancer had more types of HPV than non-cancer patients did, and among lung cancer patients, the chances of having eight types of serious HPV were significantly increased. In addition, there has been expression of HPV structural proteins by immunohistochemistry and in vitro studies that suggests HPV presence in bronchial cancer and its precursor lesions. Another study detected HPV in the EBC, bronchial brushing and neoplastic lung tissue of cases, and found a presence of an HPV infection in 16.4% of the subjects affected by non-small cell lung cancer, but in none of the controls. The reported average frequencies of HPV in lung cancers were 17% and 15% in Europe and the America, respectively, and the mean number of HPV in Asian lung cancer samples was 35.7%, with a considerable heterogeneity between certain countries and regions.

Throat cancer

In recent years, the United States has experienced an increase in the number of cases of throat cancer caused by the human papillomavirus (HPV) Type 16. Throat cancers associated with HPV have been estimated to have increased from 0.8 cases per 100,000 people in 1988 to 2.6 per 100,000 in 2004. Researchers explain this recent data by an increase in oral sex. Moreover, findings indicate this type of cancer is much more prevalent in men than in women, something that needs to be further explored. Currently, two immunizations, Gardasil and Cervarix, are recommended to girls to prevent HPV related cervical cancer but not as a precaution against HPV related throat cancer.

Genital HPVs

HPV of the genitals is the most common sexually transmitted infection globally. Most people get infected at some point in time and about 10% of women are currently infected. A large increase in the incidence of genital HPV infection occurs at the age when individuals begin to engage in sexual activity. 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. Some 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. Type 16 causes 41 to 54% of cervical cancers, and accounts for an even greater majority of HPV-induced vaginal/vulvar cancers, penile cancers, anal cancers and head and neck cancers.

Anal Cancer

Examination of squamous cell carcinoma tumor tissues from patients in Denmark and Sweden showed a high proportion of anal cancers to be positive for the types of HPV that are also associated with high risk of cervical cancer. In another study done, high-risk types of HPV, notably HPV-16, were detected in 84 percent of anal cancer specimens examined. Based on the study in Denmark and Sweden, Parkin estimated that 90% of anal cancers are attributable to HPV.[

Other



Infection with HPV has also been linked with an increased risk of cardiovascular disease.

United States of America

HPV is estimated to be the most common sexually transmitted infection in the United States. Most sexually active men and women will probably acquire genital HPV infection at some point in their lives. The American Social Health Association reported estimates that about 75â€"80% of sexually active Americans will be infected with HPV at some point in their lifetime. By the age of 50 more than 80% of American women will have contracted at least one strain of genital HPV.

It was estimated that, in the year 2000, there were approximately 6.2 million new HPV infections among Americans aged 15â€"44; of these, an estimated 74% occurred to people between ages of 15 and 24. Of the STDs studied, genital HPV was the most commonly acquired. In the United States, it is estimated that 10% of the population has an active HPV infection, 4% has an infection that has caused cytological abnormalities, and an additional 1% has an infection causing genital warts.

Estimates of HPV prevalence vary from 14% to more than 90%. One reason for the difference is that some studies report women who currently have a detectable infection, while other studies report women who have ever had a detectable infection. Another cause of discrepancy is the difference in strains that were tested for.

One study found that, during 2003â€"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; 15.2% were infected with one or more of the high-risk types that can cause cancer.

The prevalence for high-risk and low-risk types is roughly similar over time.

Human papillomavirus is not included among the diseases that are typically reportable to the CDC as of 2011.

History



In 1972, the association of the human papilloma viruses with skin cancer in epidermodysplasia verruciformis was proposed by Stefania Jabłońska in Poland. In 1978, Jabłońska and Gerard Orth at the Pasteur Institute discovered HPV-5 in skin cancer. In 1976 Harald zur Hausen published the hypothesis that human papilloma virus plays an important role in the cause of cervical cancer. In 1983 and 1984 zur Hausen and his collaborators identified HPV16 and HPV18 in cervical cancer.

The mutant HeLa cell line contains extra DNA in its genome that originated from HPV type 18.

References



External links



  • Information Centre on HPV and Cancer, ICO .
  • Demonstration by animation of HPV on YouTube
  • HPV Fact sheets, Centers for Disease Control and Prevention .
  • Myths and misconceptions about HPV, American Social Health Association .
  • HPV links to oral cancers (peer reviewed information), The Oral Cancer Foundation .
  • "STI: HPV", Young & healthy (for adolescents), CA .
  • HPV found under the fingernails of young men, The Daily (University of Washington), Aug 8, 2007 .
  • "Human Papillomavirus (HPV) Vaccines", National Cancer Institute Fact Sheet, US National Institutes of Health, October 22, 2009.
  • http://hpv.health.gov.au/ Australian HPV vaccination programme


19 comments:

  1. Replies
    1. I can’t believe this. A great testimony that i must share to all patient of [HPV] in the world. i never believed that their could be any complete cure for HUMAN PAPILLOMA VIRUS or any cure for HUMAN PAPILLOMA VIRUS, Mrs JANE introduce me to DR.AKHIGBE a herbal doctor who lives in Africa who brought him back to life again. so i had to try it too and you can,t believe that in just few weeks i started using the herbal medicine he sent to me i was perfectly ok and . Right now i can tell you that few months now i have not had any symptoms of HPV and i have just went for text last week and the doctor confirmed that there is no trace of any HPV in my body system. Glory be to God for leading me to this genuine DR.AKHIGBE I am so happy as i am sharing this testimony. My advice to you all who thinks that their is no cure for HPV that is Not true ,just contact him and get cure from DR.AKHIGBE via his Email DRAKHIGBESPELLHOME@GMAIL.COM and you will be free and free forever, Try it and you will not regret it because it truly works. One thing i have come to realize is that you never know how true it is until you try...or you can whatsapp him +2348106618681, OR Email him DRAKHIGBESPELLHOME@GMAIL.COM OR if you need my assistant via mail:jamesava001@gmail.com...
      THIS IS THE TYPE OF HERBAL MEDICATION HE HAVE
      1 Cancer
      2 Hiv
      3 Low sperm count
      4 Barrenness
      5 Hvp
      6 Herpes
      7 Genital Wart
      8 Rare disease
      9 Hepatitis
      10 Syphilis
      11 Diabetes
      God bless you sir for your good work that you done.....

      Delete
  2. hello friends I am porter dennis from U S A. God is be really good to me in my life, before people said there is no cure on H.P.V TYPE, but today many people have now believe that there is a cure FOR H.P.V/ IT can be cured through Africans root and herbs, our great doctors have finally found the cure of H.P.V, many have get cured with the help of a great spell caster known as Dr Oduwa he's the one of the great spell herbal doctor in Africa and he has the cure on this disease H.P.V/TYPE 1 TYPE 2 TYPE 3 AND TYPE 4. TYPE 5, human papilomavirus, genital warts, herpes, syphilis, cancer, hepatitis a b and c. hire blood pressures, body disease, diabetics, epilepsy, HIV aids, pregnancy,ALS and many difference kinds of diseases, last month he share is Herbal medicine in some medical hospital and now he is well recognize as one of the best spell caster in Africa, you don't have to be sad any more or share your tears any more on this disease when the cure have already be found. in 2015 the total number of people living with H.P.V was 5.8 million but today the total number is now 2.0 million, if you want to get in touch with him in private contact him on this e-mail below: dr.oduwaspellhome@gmail.com cell phone contact +2348152586912 his whatsapp contact is +2348152586912. so now contact him and get rid of your disease. immediately because this disease are not melt for us, with GOD all things are possible, so GOD has use this great dr oduwa of dr oduwa herbal center to let people no that this disease are not actually melt for us. and also here is my email address you can get in contact with me if you wish to no more about this great wonderful herbal doctor that has so much made me believe in him ok, so here is my email address porterdennis9@gmail.com thanks everybody and most especially you dr oduwa of dr.oduwaspellhome@gmail.com or droduwaspellhome@outlook.com

    ReplyDelete
  3. I can’t believe this. A great testimony that i must share to all patient of [HPV] in the world. i never believed that their could be any complete cure for HUMAN PAPILLOMA VIRUS or any cure for HUMAN PAPILLOMA VIRUS, Mrs JANE introduce me to DR.AKHIGBE a herbal doctor who lives in Africa who brought him back to life again. so i had to try it too and you can,t believe that in just few weeks i started using the herbal medicine he sent to me i was perfectly ok and . Right now i can tell you that few months now i have not had any symptoms of HPV and i have just went for text last week and the doctor confirmed that there is no trace of any HPV in my body system. Glory be to God for leading me to this genuine DR.AKHIGBE I am so happy as i am sharing this testimony. My advice to you all who thinks that their is no cure for HPV that is Not true ,just contact him and get cure from DR.AKHIGBE via his Email DRAKHIGBESPELLHOME@GMAIL.COM and you will be free and free forever, Try it and you will not regret it because it truly works. One thing i have come to realize is that you never know how true it is until you try...or you can whatsapp him +2348106618681, OR Email him DRAKHIGBESPELLHOME@GMAIL.COM OR if you need my assistant via mail:jamesava001@gmail.com...
    THIS IS THE TYPE OF HERBAL MEDICATION HE HAVE
    1 Cancer
    2 Hiv
    3 Low sperm count
    4 Barrenness
    5 Hvp
    6 Herpes
    7 Genital Wart
    8 Rare disease
    9 Hepatitis
    10 Syphilis
    11 Diabetes
    God bless you sir for your good work that you done.....

    ReplyDelete
  4. I got my first electronic cigarette kit from VaporFi, and I love it very much.

    ReplyDelete
  5. MY NAME IS WILSON KITA JOYCE FROM THE UNITED STATE OF AMERICA,I AM USING THIS GREAT OPPORTUNITY TO SAVE LIFE BY SHARING MY TESTIMONY THAT THERE IS A CURE FOR HERPES BECAUSE I AM A LIVING TESTIMONY,I SUFFERED FOR HERPES FOR GOOD ONE YEAR AND TWO MONTHS AFTER LOOSING HOPE THAT I CAN NEVER GET THE CURE BEACAUSE THE DOCTORS SAID THERE IS NO CURE FOR IT,BUT THANKS BEEN TO THIS GREAT MAN CALLED DR OKOYE OFURA WHOM I READ A TESTIMONY ABOUT ON HOW HE CURED HIV/AIDS WITH HIS HERBAL MEDICINE,I NEVER BELIEVE THIS BUT I DECIDED TO CONTACT HIM THROUGH THE STATED EMAIL,(drokoyeharbalremedy@gmail.com) and he send to me a herbal medicine and ask me to drink and bath with the herbal medicine for 1 week but to my greatest surprises, i went for a medical test after two weeks and my status was negetive till today i cant keep sharing this testimony please brothers and sisters there is a cure to HERPIS contact this man for what ever you are going through, what ever sickness you are suffering from, like
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    ReplyDelete
  6. Congratulations! This is the best thing, Thank you so much for taking the time to share this exciting information.
    hinh anh benh sui mao ga o nam gioi

    ReplyDelete
  7. Thanks to the great SABU herbalist doctor that has cured many people of HPV DISEASE today i am here to testify on his wonders on my life. for changing my life for the better after all the frustration of getting cured finally i got introduce to DR.SABU for which i believe has a cured after reading all his testimonies. after writing to him. he responded quick to me that i will be cured for my HPV DISEASE once i am able to receive his herbal medicine. afterwards he prepared my herbal cure and sent to me and when i did received it and used it. i was surprised that there was changes going on in my body. behold after using the medicine for the days he assured me that i should go and test myself. and getting there i was found HPV negative, and even the doctor was surprise and told me this can only be a miracle. i'm completely cured today and that happened by the great herbal remedy. contact DR.SABU Now on his email:drsabuspelltemple@gmail.com or his Whats-app Number :+254729840796 or his websites: https://drsabuspelltemple.wixsite.com/dr-sabu

    ReplyDelete
  8. I never believed i would be healed someday.This disease started circulate all over my body and i have been taking treatment from my doctor, few weeks ago i came on to search the internet if i could get any information concerning the prevention of this disease, on my search i saw a testimony of someone who has been healed from (HARPS and other from ALS) by this Man DR.OKABEN and she also gave the email address of this man and advise we should contact him for any sickness that he would be of help, so i wrote to dr.okabenherbalspell@gmail.com telling him about my (Hepatitis B and Skin Tag) he told me not to worry that i was going to be cured!! hmm i never believed it, well after all the procedures and remedy given to me by this man few weeks later i started experiencing changes all over me, so i went to my Doctor for test again, when the result came out, behold i was totally free from the Hepatitis B as the Doctor OKABEN assured me, So friends my advise is if you have such disease or virus like HSV, HPV, HBV,MNA, ALS Cancer or any other at all you can email DR.OKABEN Name: DR. OKABEN Email: dr.okabenherbalspell@gmail.com Tell: call +2349029519146 Whatsapp: +2349029519146

    ReplyDelete
  9. Hi viewers, my son is 28 years old was diagnosed with HPV strains 16 and 21 (after DNA analysis - HPV). It has no visible lesions of the cervix but Pap test detected changes in the cells (ASCUS and AGUS). The doctor prescribed a very good treatment with Cervugid Ovules. We repeated Pap in February, after treatment she was not cured. The last treatment she took was About 2 years ago I applied natural treatment from Dr okaben herbal centre, a week after applying the treatment all the warts were gone. it's now 2 years and some months I don't have single wart or any symptoms of hpv. wow"" it's great, Dr okaben has finally cured me. he is also specialized in the cure of the following: Cancer, HIV,ALS, MND, Low sperm count, Barrenness, Hvp, Herpes, Genital Wart, Rare disease, Hepatitis, Syphilis, Diabetes ETC His email address; dr.oluwarindetradomedicalhouse@gmail.com, call umber: +(2349029519146). I hope other patients to get better after this treatment. God bless

    ReplyDelete
  10. I am glad with the invention of natural herbal permanent cure for HIV. Sometimes last year i was checking for permanent solution to this offensive infection i got from boy friend then i came across a testimony shared by someone who got cured already and i applied E-mail; traditionalherbalhealingcentre@gmail.com or WhatsApp +2348140033827 The herbal doctor called me to ask if i actually needed the cure, i ordered and he sent me the herbs which i used for two weeks then i was totally relieved of all symptoms. Now i completely test negative to HIV. Thank you Doctor.

    ReplyDelete
  11. I am Tom Kingsley. It's been a while since I've written to thank you for my life Dr OHIKHOBO who helped me in my life. I was infected with HERPES SIMPLEX VIRUS in 2016, i went to many hospitals for cure but there was no solution, so I was thinking how can I get a solution out so that my body can be okay. One day my Aunt Rosa introduce me to Doctor OHIKHOBO having seen so many testimony online about his herbal medication to cure HERPES and gave me his email:drohikhoboherbalcenter@gmail.com , so i mail him. He told me all the things I need to do and also give me instructions to follow, which I followed properly. Before I knew what is happening after one weeks the HERPES that was in my body got vanished. so if you are you are having herpes or any kind of disease listed below *DIABETES *CANCER* HIV *STROKE *INFERTILITY *HEART DISEASE and you also want cure, you can also email him at:drohikhoboherbalcenter@gmail.com and call him via+2349053294137 or whatsapp him via +2348103601042 here is his website http://drohikhoboherbalcenter.webs.com

    ReplyDelete
  12. Hello everyone .I want to quickly drop my life stories on how a
    specialize-healer called DR muthuka cure me from HPV .A great man who have
    the root and herbs to all kind of deadly disease.i was infected with HPV
    disease by a man called Fred. I never stop blame my self for falling in
    love with him .i never think HPV can be cure with the medication doctor
    muthuka send to me until I was cure ,I saw his email on you- tube by a
    patient he have cure from herpes called FLORENCE which drop the email and
    phone contact of him that make me get cure by contacting him.i really thank
    FLORENCE for sharing her testimony on how she was cure. When I contact
    him.he prepare the herbal medication for my HPV cure and also send it to me
    in UK via DHL, that get me cure within two weeks I use it.i will still drop
    is address for you E-MAIL muthukaherbalhome@gmail.com you can still contact
    or for easy communication you can WhatSAPP him via his mobile number
    +234706143964 Below are some of the illness i know he cure: 1 Cancer 2 Hiv
    3 Low sperm count 4 Barrenness 5 Hpv 6 Herpes 7 Genital Wart 8 Rare disease
    9 Hepatitis 10 Syphilis 11 Diabetes 12 Migraine,So friends my advise is if
    you have such sickness or any other at all you can email
    muthukaherbalhome@gmail.com

    ReplyDelete
  13. I can’t believe how Dr.Zuku cure my HPV VIRUS, since three year ago i was effected with HPV VIRUS, and i have taking all manner of drugs prescribed to me from several doctors,but all my effort was wasted,i cried all day thinking on how i can be cured of this illness, i lost hope while i was looking for solution for my health,but one faithful day, i was searching the internet i came across several testimonies about Dr.Zuku and how he has cure so many effected individual ,so i try and contact his email: drzukuspelltemple@gmail.com i can't express how happy i am now after so many years. If you have this ailment or whatsoever you might be suffering from contact: drzukuspelltemple@gmail.com his Mobile number +16177296273 visit his website: https://drzukuspelltemple4.wixsite.com/mysite

    ReplyDelete
  14. I am so glad to be cured from my ALS Disease, that i have suffered for 4years and ever since i have gone to many places to seek a cure but all to no avail. until one beautiful morning when i was checking out possible remedy for my ALS Disease, then i stumbled on a testifier talking about how Dr.Zuku cure him from ALS Disease after reading through the comment, i went ahead and contacted Dr.Zuku and asked for his medicine to cure my ALS Disease, after providing the materials to prepare my cure, he sent it to me through courier service and i received it within 4days and when he instructed me about how to use it and i did, 2 weeks of usage Dr.Zuku told me to go to check my self again, and behold i was negative. Dr .Zuku email drzukuspelltemple@gmail.com Or CALL/Number:+16177296273 contact by his Blogs https://drzukuspelltemple.blogspot.co.ke/

    ReplyDelete
  15. Herpes cure with the help of herbal medication for herpes and hpv cure should contact Dr Oz

    Herpes and HPV being Sexually Transmitted Diseases (STDs) can severely restrict one’s social and love life. Many people suffering from these conditions choose to remain silent, thus living a life filled completely with loneliness and frustration. But life isn’t over yet. You can not only find support with millions of other people with the same condition. I bring to you good news that can get you a permanent cure through real and effective herbal cure.He cured me and could cure you too, here is Dr Oz contact:Email

    Ozremedycure@gmail.com

    Phone Him on +2348056391583

    ReplyDelete
  16. I has suffered for Human papillomavirus HPV) for 2years, I was given some tablets at the hospital but I refused to take it, They said I have to be on it for life so I don't want take a drugs everyday for life. No point in taking medicine everyday when u won't get cure from it and I was advice to seek for natural herbal cure, after some time I found dr unuareghe is the most trustful herbalist that have herbs to cure wicked symptom's,I emailed dr unuareghe, for 2weeks been his patient he cured my (HPV) with his herbal. I only used his natural herbs for two weeks it was 100% cure. I'm not (HPV) patient anymore. I'm happy about it i finally got cured out of this mess been in my body for 2years. I also recommend you if you're living with (HPV) or herpes symptoms i also want you to be free contact dr unuareghe with the email attach to my post dr.unuareghecuringhome@gmail.com you call or whatsapp his number +2349067894643

    ReplyDelete
  17. I can’t believe how Dr.Zuku cure my HPV VIRUS, since three year ago i was effected with HPV VIRUS, and i have taking all manner of drugs prescribed to me from several doctors,but all my effort was wasted,i cried all day thinking on how i can be cured of this illness, i lost hope while i was looking for solution for my health,but one faithful day, i was searching the internet i came across several testimonies about Dr.Zuku and how he has cure so many effected individual ,so i try and contact his email: drzukuspelltemple@gmail.com i can't express how happy i am now after so many years. If you have this ailment or whatsoever you might be suffering from contact: drzukuspelltemple@gmail.com his Mobile number +16177296273 visit his website: contact Dr Zuku Blogs https://drzukuspelltemple.blogspot.co.ke/ his website https://drzukuspelltemplewhereallkindsofproblemisbesolve.wordpress.com/contact/

    ReplyDelete
  18. I am here to give a testimony about Dr. Uyi regarding HPV who cure me from it, i want to inform the general public how i was cured from (HUMAN PAPILLOMA VIRUS) by Dr. Uyi, i visited different hospital but they gave me different type of drugs but never cured me. I was browsing through the Internet searching for remedy on HPV and i saw comment of people talking about how Dr. Uyi cure herpes virus. When i contacted him he gave me hope and said not to worry that he can totally cure me, after little discussion he proceed with the preparation of the medicine and send it to me. Today, I am so happy as i am sharing this testimony. My advice to you all who thinks that there is no cure for HPV/HSV that is Not true just contact him and get cure by Dr. Uyi, He has different type of cure to so many disease/virus. You can contact him on his Email: uyiherbalmedicationcenter@gmail.com or WhatsApp him on +2348077199766.

    ReplyDelete