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Since viruses lack ribosomes (and thus rRNA), they cannot be classified within the Three Domain Classification scheme with cellular organisms. David Baltimore derived a viral classification scheme, one that focuses on the relationship between a viral genome to how it produces its mRNA. The Baltimore Schemerecognizes seven classes of viruses.
Class I: dsDNA
DNA viruses with a dsDNA genome, like bacteriophages T4 and lambda, have a genome exactly the same as the host cell that they are infecting. For this reason, many host enzymes can be utilized for replication and/or protein production. The flow of information follows a conventional pathway: dsDNA → mRNA → protein, with a DNA-dependent RNA-polymerase producing the mRNA and the host ribosome producing the protein. The genome replication, dsDNA → dsDNA, requires a DNA-dependent DNA-polymerase from either the virus or the host cell.
The virus often employs strategies for control of gene expression, to insure that particular viral products are made at specific times in the virus replication. In the case of T4, the host RNA polymerase binds to the viral DNA and begins transcribing early genes immediately after the DNA is injected into the cell. One of the early viral proteins modifies the host RNA polymerase so that it will no longer recognize host promoters at all, in addition to moving on to transcribe genes for middle-stage viral proteins. A further modification (catalyzed by middle-stage viral proteins) further modified the RNA polymerase so it will recognize viral genes coding for late-stage proteins. This insures an orderly production of viral proteins.
The replication of several dsDNA viruses results in the production of concatemers, where several viral genomes are linked together due to short single-stranded regions with terminal repeats. As the genome is packaged into the capsid a viral endonuclease cuts the concatemer to an appropriate length.
There are several animal viruses with dsDNA genomes, such as the pox viruses and the adenoviruses. The herpesviruses have several notable features, such as the link of several members with cancer and the ability of the viruses to remain in a latent form within their host. A productive infection results in an explosive viral population, cell death, and development of disease signs, during which neurons are infected. A latent infection develops in the neurons, allowing the virus to remain undetected in the host. If the viral genome is reactivated, a productive infection results, leading to viral replication and disease signs again.
Class II: ssDNA
The flow of information for ssDNA viruses, such as the parvoviruses, will still follow the conventional pathway, to a certain extent: DNA → mRNA → protein. But the viral genome can either have the same base sequence as the mRNA (plus-strand DNA) or be complementary to the mRNA (minus-strand DNA). In the former case, a DNA strand that is complementary to the viral genome must be manufactured first, forming a double-stranded replicative form (RF). This can be used to both manufacture viral proteins and as a template for viral genome copies. For the minus-strand DNA viruses, the genome can be used directly to produce mRNA but a complementary copy will still need to be made, to serve as a template for viral genome copies.
The replicative form can be used for rolling-circle replication, where one strand is nicked and replication enzymes are used to extend the free 3’ end. As a complementary strand is synthesized around the circular DNA, the 5’ end is peeled off, leading to a displaced strand that continues to grow in length.
Class VII: DNA viruses that use reverse transcriptase
The hepadnaviruses contain a DNA genome that is partially double-stranded, but contains a single-stranded region. After gaining entrance into the cell’s nucleus, host cell enzymes are used to fill in the gap with complementary bases to form a dsDNA closed loop. Gene transcription yields a plus-strand RNA known as the pregenome, as well as the viral enzyme reverse transcriptase, an RNA-dependent DNA-polymerase. The pregenome is used as a template for the reverse transcriptase to produced minus-strand DNA genomes, with a small piece of pregenome used as a primer to produce the double-stranded region of the genomes.
Class III: dsRNA
Double-stranded RNA viruses infect bacteria, fungi, plants, and animals, such as the rotavirus that causes diarrheal illness in humans. But cells do not utilize dsRNA in any of their processes and have systems in place to destroy any dsRNA found in the cell. Thus the viral genome, in its dsRNA form, must be hidden or protected from the cell enzymes. Cells also lack RNA-dependent RNA-polymerases, necessary for replication of the viral genome so the virus must provide this enzyme itself. The viral RNA-dependent RNA polymerase acts as both a transcriptase to transcribe mRNA, as well as a replicase to replicate the RNA genome.
For the rotavirus, the viral nucleocapsid remains intact in the cytoplasm with replication events occurring inside, allowing the dsRNA to remain protected. Messenger RNA is transcribed from the minus-strand of the RNA genome and then translated by the host ribosome in the cytoplasm. Viral proteins aggregate to form new nucleocapsids around RNA replicase and plus-strand RNA. The minus-strand RNA is then synthesized by the RNA replicase within the nucleocapsid, once again insuring protection of the dsRNA genome.
Class IV: +ssRNA
Viruses with plus-strand RNA, such as poliovirus, can use their genome directly as mRNA with translation by the host ribosome occurring as soon as the unsegmented viral genome gains entry into the cell. One of the viral genes expressed yields an RNA-dependent RNA-polymerase (or RNA replicase), which creates minus-strand RNA from the plus-strand genome. The minus-strand RNA can be used as a template for more plus-strand RNA, which can be used as mRNA or as genomes for the newly forming viruses.
Translation of the poliovirus genome yields a polyprotein, a large protein with protease activity that cleaves itself into three smaller proteins. Additional cleavage activity eventually yields all the proteins needed for capsid formation, as well as an RNA-dependent RNA-polymerase.
The formation of a polyprotein that is cut into several smaller proteins illustrates one possible strategy to an issue faced by many +ssRNA viruses – how to generate multiple proteins from an unsegmented +ssRNA genome? Other possibilities include:
- subgenomic mRNA – during translation, portions of the viral RNA may be skipped, resulting in different proteins than what is made from the viral RNA in its entirety.
- ribosomal frame-shifting – the ribosome “reads” the mRNA in groups of three nucleotides or codon, which translate to one amino acid. If the ribosome starts with nucleotide #1, that is one open reading frame (ORF), resulting in one set of amino acids. If the ribosome were to move forward where nucleotide 2 is the starting nucleotide that would be ORF #2, resulting in a completely different set of amino acids. If the ribosome were to move forward again where nucleotide 3 is the starting nucleotide that would be ORF#3, resulting in an entirely different set of amino acids. Some viruses have viral genes that deliberately overlap within different ORFs, leading to the production of different proteins from a single mRNA.
- readthrough mechanism – a viral genome can have stop codons embedded throughout the sequence. When the ribosome comes to a stop codon it can either stop, ending the amino acid sequence, or it can ignore the stop codon, continuing on to make a longer string of amino acids. For viruses with the readthrough mechanism, they acquire a variety of proteins by having stop codons that are periodically ignored. Sometimes this function is combined with the ribosomal frame-shifting to produce an even greater variety of viral proteins.
Class V: -ssRNA
Minus-strand RNA viruses include many members notable for humans, such as influenza virus, rabies virus, and Ebola virus. Since the genome of minus-strand RNA viruses cannot be used directly as mRNA, the virus must carry an RNA-dependent RNA-polymerase within its capsid. Upon entrance into the host cell, the plus-strand RNAs generated by the polymerase are used as mRNA for protein production. When viral genomes are needed the plus-strand RNAs are used as templates to make minus-strand RNA.
Class VI: +ssRNA, retroviruses
Despite the fact that the retroviral genome is composed of +ssRNA, it is not used as mRNA. Instead, the virus uses its reverse transcriptase to synthesize a piece of ssDNA complementary to the viral genome. The reverse transcriptase also possesses ribonuclease activity, which is used to degrade the RNA strand of the RNA-DNA hybrid. Lastly, the reverse transcriptase is used as a DNA polymerase to make a complementary copy to the ssDNA, yielding a dsDNA molecule. This allows the virus to insert its genome, in a dsDNA form, into the host chromosome, forming a provirus. Unlike a prophage, a provirus can remain latent indefinitely or cause the expression of viral genes, leading to the production of new viruses. Excision of the provirus does not occur for gene expression.
Other Infectious Agents
Viroids are small, circular ssRNA molecules that lack protein. These infectious molecules are associated with a number of plant diseases. Since ssRNA is highly susceptible to enzymatic degradation, the viroid RNA has extensive complementary base pairing, causing the viroid to take on a hairpin configuration that is resistant to enzymes. For replication viroids rely on a plant RNA polymerase with RNA replicase activity.
Prions are infectious agents that completely lack nucleic acid of any kind, being made entirely of protein. They are associated with a variety of diseases, primarily in animals, although a prion has been found that infects yeast (!). Diseases include bovine spongiform encephalopathy (BSE or “mad cow disease”), Creutzfeld-Jakob disease in humans, and scrapie in sheep.
The prion protein is found in the neurons of healthy animals (PrPC or Prion Protein Cellular), with a particular secondary structure. The pathogenic form (PrPSC or Prion Protein Scrapie) has a different secondary structure and is capable of converting the PrPC into the pathogenic form. Accumulation of the pathogenic form causes destruction of brain and nervous tissue, leading to disease symptoms such as memory loss, lack of coordination, and eventually death.
Prions. Joannamasel at English Wikipedia [CC BY-SA 3.0], via Wikimedia Commons
Baltimore Scheme, Class I, Class II, Class III, Class IV, Class V, Class VI, Class VII, DNA-dependent RNA polymerase, DNA-dependent DNA-polymerase, concatemer, productive infection, latent infection, plus-strand DNA/+DNA, minus-strand DNA/-DNA, dsDNA, ssDNA, replicative form (RF), rolling-circle replication, pregenome, reverse transcriptase, RNA-dependent DNA-polymerase, dsRNA, RNA-dependent RNA-polymerase, transcriptase, replicase, plus-strand RNA/+ssRNA, minus-strand RNA/-ssRNA, polyprotein, subgenomic mRNA, ribosomal frame-shifting, open reading frame (ORF), readthrough mechanism, stop codon, retrovirus, ribonuclease, provirus, viroid, prion, PrPC/Prion Protein Cellular, PrPSC/Prion Protein Scrapie.
- What is the Baltimore system of classification? What viral characteristics does it use?How does each viral group make proteins and replicate their genome? Where do the necessary components come from? (virus or host cell) What modifications are necessary, for viruses with a genome different from the host cell?
- What strategy do dsDNA viruses use for control of gene expression? What are concatemers? What are productive and latent infections?
- What is a replicative form? What is rolling circle replication? What is the advantage of these viral mechanisms?
- What is a pregenome? What is reverse transcriptase? What role does it play for the Class VII viruses?
- What issues do dsRNA viruses face? How do they overcome these issues? What is a transcriptase? What is a replicase?
- How is the genome used by Class IV +ssRNA viruses? What are the strategies used by these viruses to generate multiple proteins from an unsegmented genome?
- What steps are necessary for the –ssRNA viruses?
- How do the retroviruses, as +ssRNA viruses, differ from the Class IV viruses? What is a ribonuclease? What is a provirus?
- What is a viroid? What is a prion? How do these agents cause disease? How do they replicate?
Exploratory Questions (OPTIONAL)
- Why were scientists initially so resistant to the idea of prions lacking any type of nucleic acid?
The virus that isn’t there, genetic sequencing, and the magic trick
Recently, I’ve written a series of articles revealing that the existence of the SARS-CoV-2 virus is unproven.
I’ve quoted key CDC and study documents that confess “the virus is unavailable.” Which is like an ice company saying they have no access to water.     
I’ve published quotes from Dr. Tom Cowan’s major article   exposing how CDC journal authors “assemble” the idea of a virus from cobbled sequences they ASSUME are parts of SARS-CoV-2. (Below, I reprint my article on Dr. Cowan’s shocking findings.)
Now, I want to make overall comments on the con, the game, the hustle.
The public, and most medical professionals, are awed by the whole concept of genetic sequencing. They accept the process as a holy of holies. If researchers in their lab claim they’ve “sequenced the virus,” the virus must exist. How else could its genetic structure have been discovered?
Of course, the virus doesn’t have to exist at all. We are talking about an illusion. Stage magic.
And if we could force him to explain his trick, the magician would say:
“Notice, I begin with a fragment of RNA I assume is part of a larger new virus. My assumption isn’t proven. I simply make the claim.”
“Then I lay out the genetic structure of that little piece of RNA, and I discover I need a great more genetic information to fill out the sequence of the whole virus.”
“That’s not really a discovery. I already knew I’d need much more. The question is: where am I going to get that added information?”
“The answer is: from data bases. These bases contain miles of sequences that have already been established—rightly or wrongly. Sequences of other viruses.”
“Which sequences do I choose? I make guesses. I make assumptions. Actually, I choose according to a story line that has already been laid down. In this case, a story about a member of the coronavirus family. That’s right. I always knew what I was going to look for. In fact, that initial piece of RNA I began with? I could have selected all sorts of other pieces of RNA, but I chose that one because it seemed to be from the coronavirus family.”
“Does this whole business sound like a Lego or tinker-toy operation? Well, it is. I never have a physical specimen of the virus. I never isolate the purported virus from all the material that surrounds it. I just assume or pretend the virus is in there.”
“Anyway, I now select all sorts of genetic sequences from the huge database. And I hook the sequences together, AS IF they were already connected and real and waiting for me to find them. They weren’t, but I pretend they were.”
“That pretense is the key. It’s like selling a sucker a map leading to a lost silver mine. There was never a map. The con artist cobbled it together from pieces of other old maps of a territory in the mountains of Colorado. The map looks real. It looks whole. But it was never whole.”
“THE GENETIC SEQUENCE OF THE VIRUS is that map. It’s made to look like a one long code that was there all along. But it wasn’t. It isn’t.”
“Every good magic trick works this way. The magician makes the audience believe he is performing one smooth operation. But he isn’t. He’s taking all sorts of detours. He’s reaching into his sleeve and pulling out a card. He’s palming that card so no one sees it. He’s slipping the card into the deck in his other hand. And all the while, he’s talking confidently and making other gestures to distract the audience.”
“The whole purpose of the trick is to inspire awe. In the lab, the same principle applies. The researchers SEEM to find one long genetic sequence of the whole virus. Astonishing.”
“But that’s not what happened. Not by a long shot.”
“And notice one other very important thing. In the lab, we are actually piecing and cobbling together the pattern—the code—of a virus. We don’t have to deal with actual genes. What we do is all on the level of IDEATIONAL construction. We’re hooking up DATA. So that’s another level of the trick. We’re not stringing together pieces of material. We’re stringing together pieces of data from genetic databases. This would be like standing on stage in front of an audience and doing a very clever card trick without having a deck of cards in the first place. Now THAT’S a trick for the ages.”
With all this I mind, read my previous article on Dr. Tom Cowan’s shocking discoveries:
Dr. Tom Cowan explores the COVID virus invented out of sheer nonsense
—Cowan analyzes yet another key document posted by the CDC, in their journal, Emerging Infectious Diseases: “Severe Acute Respiratory Syndrome Coronavirus 2 from Patient with Coronavirus Disease, United States”—
The hits keep coming. The CDC used an arbitrary computer “tinker-toy” process to invent a description of the virus. The virus that no one has proven exists. This is the basic conclusion of Dr. Tom Cowan.
The CDC article  was discovered by Sally Fallon Morrell. Her co-author, Dr. Cowan, fleshes out the fraud. Cowan’s article is titled, “Only Poisoned Monkey Cells ‘Grew’ the ‘Virus’.”  
Dr. Cowan: “[The CDC journal article] was published in June 2020 [original publication, March 2020]. The purpose of the article was for a group of about 20 virologists to describe the state of the science of the isolation, purification and biological characteristics of the new SARS-CoV-2 virus, and to share this information with other scientists for their own research. A thorough and careful reading of this important paper reveals some shocking findings.”
“First, in the section titled ‘Whole Genome Sequencing,’ we find that rather than having isolated the virus and sequencing the genome from end to end, they found 37 base pairs from unpurified samples using PCR probes. This means they actually looked at 37 out of the approximately 30,000 of the base pairs that are claimed to be the genome of the intact virus. They then took these 37 segments and put them into a computer program, which filled in the rest of the base pairs.”
In other words, the sequencing of the SARS-CoV-2 virus was done by assumption and arbitrary inference. If this is science, a penguin is a spaceship.
Cowan: “To me, this computer-generation step constitutes scientific fraud. Here is an equivalency: A group of researchers claim to have found a unicorn because they found a piece of a hoof, a hair from a tail, and a snippet of a horn. They then add that information into a computer and program it to re-create the unicorn, and they then claim this computer re-creation is the real unicorn. Of course, they had never actually seen a unicorn so could not possibly have examined its genetic makeup to compare their samples with the actual unicorn’s hair, hooves and horn.”
“The researchers claim they decided which is the real genome of SARS-CoV-2 by ‘consensus,’ sort of like a vote. Again, different computer programs will come up with different versions of the imaginary ‘unicorn,’ so they come together as a group and decide which is the real imaginary unicorn.”
As I’ve been stating , the “discovery” of the “new virus” was actually the foisting of a PRE-DETERMINED STORY ABOUT A VIRUS. Nothing real or believable about it.
But once the official pattern is laid down, others follow it dutifully.
Dr. Cowan uncovers more insanity in the CDC journal article. Using the ASSUMED new virus, in an UN-ISOLATED STATE, the researchers try to prove it is harmful by injecting it on to several different types of cells in the lab:
Cowan: “The real blockbuster finding in this study comes later, a finding so shocking that I had to read it many times before I could believe what I was reading. Let me quote the passage intact:”
“’Therefore, we examined the capacity of SARS-CoV-2 to infect and replicate in several common primate and human cell lines, including human adenocarcinoma cells (A549), human liver cells (HUH 7.0), and human embryonic kidney cells (HEK-293T). In addition to Vero E6 and Vero CCL81 cells [monkey cells]. … Each cell line was inoculated at high multiplicity of infection and examined 24h post-infection. No CPE was observed in any of the cell lines except in Vero [monkey] cells, which grew to greater than 10 to the 7th power at 24 h post-infection. In contrast, HUH 7.0 and 293T showed only modest viral replication, and A549 cells [human cells] were incompatible with SARS CoV-2 infection’.”
“What does this language actually mean, and why is it the most shocking statement of all from the virology community? When virologists attempt to prove infection, they have three possible ‘hosts’ or models on which they can test…”
“The third method virologists use to prove infection and pathogenicity — the method they most rely on — is inoculation of solutions they say contain the virus onto a variety of tissue cultures. As I have pointed out many times, such inoculation has never been shown to kill (lyse) the tissue, unless the tissue is first starved and poisoned.”
“The shocking thing about the above [CDC journal] quote is that using their own methods, the virologists found that solutions containing SARS-CoV-2 — even in high amounts — were NOT, I repeat NOT, infective to any of the three human tissue cultures they tested. In plain English, this means they proved, on their terms, that this ‘new coronavirus’ is not infectious to human beings. It is ONLY infective to monkey kidney cells, and only then when you add two potent drugs (gentamicin and amphotericin), known to be toxic to kidneys, to the mix.”
“My friends, read this again and again. These virologists, published by the CDC, performed a clear proof, on their terms, showing that the SARS-CoV- 2 virus is harmless to human beings. That is the only possible conclusion, but, unfortunately, this result is not even mentioned in their conclusion. They simply say they can provide virus stocks cultured only on monkey Vero cells, thanks for coming.”
So first…use a process of genetic sequencing that involves concocting, out of an arbitrary computer program…
The existence and structure of the “new virus”…
And then, taking a soup that the researchers claim contains the virus, in an un-isolated state, inject the soup into several types of cells in the lab…
And discover the prime target—human cells—are not infected by the imaginary virus.
And after this good day’s work, walk away and pretend nothing odd or self-incriminating happened.
And oh yes, lock down the planet based on this “science.”
Naturally, we MUST take a toxic vaccine that prevents non-infection by the non-virus.
The Molecular Biology of Coronaviruses
Coronaviruses are large, enveloped RNA viruses of both medical and veterinary importance. Interest in this viral family has intensified in the past few years as a result of the identification of a newly emerged coronavirus as the causative agent of severe acute respiratory syndrome (SARS). At the molecular level, coronaviruses employ a variety of unusual strategies to accomplish a complex program of gene expression. Coronavirus replication entails ribosome frameshifting during genome translation, the synthesis of both genomic and multiple subgenomic RNA species, and the assembly of progeny virions by a pathway that is unique among enveloped RNA viruses. Progress in the investigation of these processes has been enhanced by the development of reverse genetic systems, an advance that was heretofore obstructed by the enormous size of the coronavirus genome. This review summarizes both classical and contemporary discoveries in the study of the molecular biology of these infectious agents, with particular emphasis on the nature and recognition of viral receptors, viral RNA synthesis, and the molecular interactions governing virion assembly.
Influenza Virus Resource help center
Influenza viruses belong to the family Orthomyxoviridae. The viral particles are about 80-120 nm in diameter and can be spherical or pleomorphic. They have a lipid membrane envelope that contains the two glycoproteins: hemagglutinin (HA) and neuraminidase (NA). These two proteins determine the subtypes of Influenza A virus. There are 18 H subtypes and 11 N subtypes.
The Influenza A viral genome consists of eight, single negative-strand RNAs that can range between 890 and 2340 nucleotides long. Each RNA segment encodes one to two proteins. Find more about the replication of Influenza A virus here.
Influenza A virus particles. Courtesy of Audray Harris, Bernard Heymann and Alasdair C. Steven, LSBR, NIAMS, NIH.
Flu epidemics cause morbidity and mortality worldwide. Each year in the USA, more than 200,000 patients are admitted to hospitals because of influenza and there are approximately 36,000 influenza-related deaths.
Of the three types of influenza virus-A, B and C-the A and B types can cause flu epidemics. Influenza A virus is found in human and many other animals. There are over 100 subtypes of Influenza A virus. All subtypes have been found in wild birds, which are thought to be a natural reservoir of Influenza A virus and the source of influenza A viruses in all other animals.
Some HPV types, such as HPV-5, may establish infections that persist for the lifetime of the individual without ever manifesting any clinical symptoms. HPV types 1 and 2 can cause common warts in some infected individuals.  HPV types 6 and 11 can cause genital warts and laryngeal papillomatosis. 
Many HPV types are carcinogenic.  The table below lists common symptoms of HPV infection and the associated strains of HPV.
- Highest risk:  16, 18, 31, 45
- Other high-risk:  33, 35, 39, 51, 52, 56, 58, 59
- Probably high-risk:  26, 53, 66, 68, 73, 82
Skin infection ("cutaneous" infection) with HPV is very widespread.  Skin infections with HPV can cause noncancerous skin growths called warts (verrucae). Warts are caused by a rapid growth of cells on the outer layer of the skin.  While cases of warts have been described since the time of ancient Greece, their viral cause was not known until 1907. 
Skin warts are most common in childhood and typically appear and regress spontaneously over the course of weeks to months. Recurring skin warts are common.  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 an individual may become resistant to one HPV type while remaining susceptible to other types. [ citation needed ]
- are usually 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. are found on the soles of the feet they 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 are more difficult to treat than warts in other locations.  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. 
Common, flat, and plantar warts are much less likely to spread from person to person.
Genital warts Edit
HPV infection of the skin in the genital area is the most common sexually transmitted infection worldwide.  Such infections are associated with genital or anal warts (medically known as condylomata acuminata or venereal warts), and these warts are the most easily recognized sign of genital HPV infection. [ citation needed ]
The strains of HPV that can cause genital warts are usually different from those that cause warts on other parts of the body, such as the hands or feet, or even the inner thighs. A wide variety of HPV types can cause genital warts, but types 6 and 11 together account for about 90% of all cases.   However, in total more than 40 types of HPV are transmitted through sexual contact and can infect the skin of the anus and genitals.  Such infections may cause genital warts, although they may also remain asymptomatic. [ citation needed ]
The great majority of genital HPV infections never cause any overt symptoms and are cleared by the immune system in a matter of months. Moreover, people may transmit the virus to others even if they do not display overt symptoms of infection. Most people acquire genital HPV infections at some point in their lives, 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. As with cutaneous HPVs, immunity to genital HPV is believed to be specific to a specific strain of HPV. [ citation needed ]
Laryngeal papillomatosis Edit
In addition to genital warts, infection by HPV types 6 and 11 can cause a rare condition known as recurrent laryngeal papillomatosis, in which warts form on the larynx  or other areas of the respiratory tract.   These warts can recur frequently, may interfere with breathing, and in extremely rare cases can progress to cancer. For these reasons, repeated surgery to remove the warts may be advisable.  
Virus types Edit
About a dozen HPV types (including types 16, 18, 31, and 45) are called "high-risk" types because persistent infection has been linked to cancer of the oropharynx,  larynx,  vulva, vagina, cervix, penis, and anus.   These cancers all involve sexually transmitted infection of HPV to the stratified epithelial tissue.    Individuals infected with both HPV and HIV have an increased risk of developing cervical or anal cancer.  HPV type 16 is the strain most likely to cause cancer and is present in about 47% of all cervical cancers,   and in many vaginal and vulvar cancers,  penile cancers, anal cancers, and cancers of the head and neck. 
Case statistics Edit
An estimated 561,200 new cancer cases worldwide (5.2% of all new cancers) were attributable to HPV in 2002, making HPV one of the most important infectious causes of cancer.  HPV-associated cancers make up over 5% of total diagnosed cancer cases worldwide, and this incidence is higher in developing countries where it is estimated to cause almost half a million cases each year. 
In the United States, about 30,700 cases of cancer due to HPV occur each year. 
|Cancer area||Average annual number of cases||HPV attributable (estimated)||HPV 16/18 attributable (estimated)|
Cancer development Edit
In some infected individuals, their immune systems may fail to control HPV. Lingering infection with high-risk HPV types, such as types 16, 18, 31, and 45, can favor the development of cancer.  Co-factors such as cigarette smoke can also enhance the risk of such HPV-related cancers.  
HPV is believed to cause cancer by integrating its genome into nuclear DNA. Some of the early genes expressed by HPV, such as E6 and E7, act as oncogenes that promote tumor growth and malignant transformation.  HPV genome integration can also cause carcinogenesis by promoting genomic instability associated with alterations in DNA copy number. 
E6 produces a protein (also called E6) that binds to and inactivates a protein in the host cell called p53. Normally, p53 acts to prevent cell growth, and promotes cell death in the presence of DNA damage. 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 protein that arrests the cell cycle and prevents cell growth and survival when DNA damage occurs. Thus, inactivation of p53 by E6 can promote unregulated cell division, cell growth, and cell survival, characteristics of cancer. [ citation needed ]
E6 also has a close relationship with the cellular protein E6-associated protein (E6-AP), which 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. [ citation needed ]
Squamous cell carcinoma of the skin Edit
Studies have also shown a link between a wide range of HPV types and squamous cell carcinoma of the skin. In such cases, in vitro studies suggest that the E6 protein of the HPV virus may inhibit apoptosis induced by ultraviolet light. 
Cervical cancer Edit
Nearly all cases of cervical cancer are associated with HPV infection, with two types, HPV16 and HPV18, present in 70% of cases.       In 2012, twelve HPV types were considered carcinogenic for cervical cancer by the International Agency for Research on Cancer: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59.  HPV is necessary for cervical cancer to occur.  Persistent HPV infection increases the risk for developing cervical carcinoma. Individuals who have an increased incidence of these types of infection are women with HIV/AIDS, who are at a 22-fold increased risk of cervical cancer.  
The carcinogenic HPV types in cervical cancer belong to the alphapapillomavirus genus and can be grouped further into HPV clades.  The two major carcinogenic HPV clades, alphapapillomavirus-9 (A9) and alphapapillomavirus-7 (A7), contain HPV16 and HPV18, respectively.  These two HPV clades were shown to have different effects on tumour molecular characteristics and patient prognosis, with clade A7 being associated with more aggressive pathways and an inferior prognosis. 
In 2012, about 528,000 new cases and 266,000 deaths from cervical cancer occurred worldwide.  Around 85% of these occurred in the developing world. 
Most HPV infections of the cervix are cleared rapidly by the immune system and do not progress to cervical cancer (see below the 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).   Furthermore, both the HPV infection and cervical cancer drive metabolic modifications that may be correlated with the aberrant regulation of enzymes related to metabolic pathways. 
Non-European (NE) HPV16 variants are significantly more carcinogenic than European (E) HPV16 variants. 
Anal cancer Edit
Studies show a link between HPV infection and anal cancers. Sexually transmitted HPVs are found in a large percentage of anal cancers.  Moreover, the risk for anal cancer is 17 to 31 times higher among HIV-positive individuals who were coinfected with high-risk HPV, and 80 times higher for particularly HIV-positive men who have sex with men. 
Anal Pap smear screening for anal cancer might benefit some subpopulations of men or women engaging in anal sex.  No consensus exists, though, that such screening is beneficial, or who should get an anal Pap smear.  
Penile cancer Edit
HPV is associated with approximately 50% of penile cancers. In the United States, penile cancer accounts for about 0.5% of all cancer cases in men. HPV16 is the most commonly associated type detected. The risk of penile cancer increases 2- to 3-fold for individuals who are infected with HIV as well as HPV. 
Head and neck cancers Edit
Oral infection with high-risk carcinogenic HPV types (most commonly HPV 16)  is associated with an increasing number of head and neck cancers.     This association is independent of tobacco and alcohol use.   
Sexually transmitted forms of HPV account for about 25% of cancers of the mouth and upper throat (the oropharynx) worldwide,  but the local percentage varies widely, from 70% in the United States  to 4% in Brazil.  Engaging in anal or oral sex with an HPV-infected partner may increase the risk of developing these types of cancers. 
In the United States, the number of newly diagnosed, HPV-associated head and neck cancers has surpassed that of cervical cancer cases.  The rate of such cancers has increased from an estimated 0.8 cases per 100,000 people in 1988  to 4.5 per 100,000 in 2012,  and, as of 2015, the rate has continued to increase.  Researchers explain these recent data by an increase in oral sex. This type of cancer is more common in men than in women. 
The mutational profile of HPV-positive and HPV-negative head and neck cancer has been reported, further demonstrating that they are fundamentally distinct diseases. 
Lung cancer Edit
Some evidence links HPV to benign and malignant tumors of the upper respiratory tract. The International Agency for Research on Cancer has 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 noncancer patients did, and among lung cancer patients, the chances of having eight types of serious HPV were significantly increased.  In addition, expression of HPV structural proteins by immunohistochemistry and in vitro studies suggest 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 nonsmall 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 Americas, respectively, and the mean number of HPV in Asian lung cancer samples was 35.7%, with a considerable heterogeneity between certain countries and regions. 
Skin cancer Edit
In very rare cases, HPV may cause epidermodysplasia verruciformis (EV) in individuals with a weakened immune system. The virus, unchecked by the immune system, causes the overproduction of keratin by skin cells, resulting in lesions resembling warts or cutaneous horns which can ultimately transform into skin cancer, but the development is not well understood.   The specific types of HPV that are associated with EV are HPV5, HPV8, and HPV14. 
Sexually transmitted HPV is divided into two categories: low-risk and high-risk. Low-risk HPVs cause warts on or around the genitals. Type 6 and 11 cause 90% of all genital warts and recurrent respiratory papillomatosis that causes benign tumors in the air passages. High-risk HPVs cause cancer and consist of about a dozen identified types. Type 16 and 18 are two that are responsible for causing most of HPV-caused cancers. These high-risk HPVs cause 5% of the cancers in the world. In the United States, high-risk HPVs cause 3% of all cancer cases in women and 2% in men. 
Risk factors for persistent genital HPV infections, which increases the risk for developing cancer, include early age of first sexual intercourse, multiple partners, smoking, and immunosuppression.  Genital HPV is spread by sustained direct skin-to-skin contact, with vaginal, anal, and oral sex being the most common methods.   Occasionally it can spread from a mother to her baby during pregnancy. HPV is difficult to remove via standard hospital disinfection techniques, and may be transmitted in a healthcare setting on re-usable gynecological equipment, such as vaginal ultrasound transducers.  The period of communicability is still unknown, but probably at least as long as visible HPV lesions persist. HPV may still be transmitted even after lesions are treated and no longer visible or present. 
Although genital HPV types can be transmitted from mother to child during birth, the appearance of genital HPV-related diseases in newborns is rare. However, the lack of appearance does not rule out asymptomatic latent infection, as the virus has proven to be capable of hiding for decades. 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%. [ citation needed ]
Genital infections Edit
Genital HPV infections are transmitted primarily by contact with the genitals, anus, or mouth of an infected sexual partner. 
Of the 120 known human papilloma viruses, 51 species and three subtypes infect the genital mucosa.  Fifteen are classified as high-risk types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82), three as probable high-risk (26, 53, and 66), and twelve as low-risk (6, 11, 40, 42, 43, 44, 54, 61, 70, 72, 81, and 89). 
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. 
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 twenty-five heterosexual couples every other month for an average of seven months. She found two couples where the man's genitals infected the woman's hand with high-risk HPV, two where her hand infected his genitals, one where her genitals infected his hand, two each where he infected his own hand, and she infected her own hand.   Hands were not the main source of transmission in these twenty-five couples, but they were significant. [ citation needed ]
Partridge reports men's fingertips became positive for high risk HPV at more than half the rate (26% per two years) as their genitals (48%).  Winer reports 14% of fingertip samples from sexually active women were positive. 
Non-sexual hand contact seems to have little or no role in HPV transmission. Winer found all fourteen 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 Edit
Sharing of possibly contaminated objects, for example, razors,  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.  
Though it has traditionally been assumed that HPV is not transmissible via blood—as it is thought to only infect cutaneous and mucosal tissues—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. 
Hospital transmission of HPV, especially to surgical staff, has been documented. Surgeons, including urologists and/or anyone in the room, is subject to HPV infection by inhalation of noxious viral particles during electrocautery or laser ablation of a condyloma (wart).  There has been a case report of a laser surgeon who developed extensive laryngeal papillomatosis after providing laser ablation to patients with anogenital condylomata. 
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 12–24 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 the 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. HPV 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 double-stranded circular 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, laminins, and annexin A2  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 of 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. [ citation needed ]
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 Edit
The two primary oncoproteins of high risk HPV types are E6 and E7. The “E” designation indicates that these two proteins are early proteins (expressed early in the HPV life cycle), while the "L" designation indicates that they are late proteins (late expression).  The HPV genome is composed of six early (E1, E2, E4, E5, E6, and E7) open reading frames (ORF), 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. 
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. 
Latency period Edit
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. 
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). [ citation needed ]
|Months after initial positive test||8 months||12 months||18 months|
|% of men tested negative||70%||80%||100%|
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." 
Over 170 types of HPV have been identified, and they are designated by numbers.   They may be divided into "low-risk" and "high-risk" types. Low-risk types cause warts and high-risk types can cause lesions or cancer.  
Cervical testing Edit
Guidelines from the American Cancer Society recommend different screening strategies for cervical cancer based on a woman's age, screening history, risk factors and choice of tests.  Because of the link between HPV and cervical cancer, the ACS currently recommends early detection of cervical cancer in average-risk asymptomatic adults primarily with cervical cytology by Pap smear, regardless of HPV vaccination status. Women aged 30–65 should preferably be tested every 5 years with both the HPV test and the Pap test. In other age groups, a Pap test alone can suffice unless they have been diagnosed with atypical squamous cells of undetermined significance (ASC-US).  Co-testing with a Pap test and HPV test is recommended because it decreases the rate of false-negatives. According to the National Cancer Institute, "The most common test detects DNA from several high-risk HPV types, but it cannot identify the types 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. [ citation needed ]
"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." 
Mouth testing Edit
Guidelines for oropharyngeal cancer screening by the Preventive Services Task Force and American Dental Association in the U.S. suggest conventional visual examination, but because some parts of the oropharynx are hard to see, this cancer is often only detected in later stages. 
The diagnosis of oropharyngeal cancer occurs by biopsy of exfoliated cells or tissues. The National Comprehensive Cancer Network and College of American Pathologists recommend testing for HPV in oropharyngeal cancer.  However, while testing is recommended, there is no specific type of test used to detect HPV from oral tumors that is currently recommended by the FDA in the United States. Because HPV type 16 is the most common type found in oropharyngeal cancer, p16 immunohistochemistry is one test option used to determine if HPV is present,  which can help determine course of treatment since tumors that are negative for p16 have better outcomes. Another option that has emerged as a reliable option is HPV DNA in situ hybridization (ISH) which allows for visualization of the HPV. 
Testing men Edit
There is not a wide range of tests available even though HPV is common most studies of HPV used tools and custom analysis not available to the general public.  [ needs update ] Clinicians often 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.   [ needs update ] 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. 
Studies have tested for and found HPV in men, including high-risk types (i.e. the types found in cancers), on fingers, mouth, saliva, anus, urethra, urine, semen, blood, scrotum and penis. 
The Qiagen/Digene kit mentioned in the previous section was used successfully off label to test the penis, scrotum and anus  of men in long-term relationships with women who were positive for high-risk HPV. 60% of them were found to carry the virus, primarily on the penis.  [ needs update ] Other studies used cytobrushes and custom analysis.   [ needs update ]
In one study researchers sampled subjects' urethra, scrotum and penis.   [ needs update ] Samples taken from 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, along with the scrotum, since sampling the urethra or anus added very little to the diagnosis.  Dunne recommends the glans, shaft, their crease, and the foreskin. 
In one study the subjects were asked not to wash their genitals for 12 hours before sampling, including the urethra as well as the scrotum and the penis.  Other studies are silent on washing - a particular gap in studies of the hands. [ citation needed ]
One small study used wet cytobrushes, rather than wet the skin.  It found a higher proportion of men to be HPV-positive when the skin was rubbed with a 600 grit emery paper before being swabbed with the brush, rather than swabbed with no preparation. It's unclear whether the emery paper collected the virions or simply loosened them for the swab to collect.
Studies have found self-collection (with emery paper and Dacron swabs) as effective as collection done by a clinician, and sometimes more so, since patients were more willing than a clinician to scrape vigorously.  [ needs update ]  Women had similar success in self-sampling using tampons, swabs, cytobrushes and lavage.  [ needs update ]
Several studies used cytobrushes to sample fingertips and under fingernails, without wetting the area or the brush.    [ needs update ]
Other studies analyzed urine, semen, and blood and found varying amounts of HPV,  but there is not a publicly available test for those yet.
Other testing Edit
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 [ citation needed ] 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. [ citation needed ] At this time, HPV tests for males are used only in research. [ citation needed ]
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 has not been proven, as there has not been a FDA approved product as of August 2018  testing by blood would be a less invasive test for screening purposes.
The HPV vaccines can prevent the most common types of infection.  To be effective they must be used before an infection occurs and are therefore recommended between the ages of nine and thirteen. Cervical cancer screening, such as with the Papanicolaou test (pap) or looking at the cervix after using acetic acid, can detect early cancer or abnormal cells that may develop into cancer. This allows for early treatment which results in better outcomes.  Screening has reduced both the number and deaths from cervical cancer in the developed world.  Warts can be removed by freezing. 
Three vaccines are available to prevent infection by some HPV types: Gardasil, Gardasil 9 and Cervarix all three 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. Gardasil 9 is nonavalent, it has the potential to prevent about 90% of cervical, vulvar, vaginal, and anal cancers. It can protect for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 the latter five cause up to 20% of cervical cancers which were not previously covered. 
The vaccines provide little benefit to women already 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. 
There is high-certainty evidence that HPV vaccines protect against precancerous cervical lesions in young women, particularly those vaccinated aged 15 to 26.  HPV vaccines do not increase the risk of serious adverse events.  Longer follow-up is needed to monitor the impact of HPV vaccines on cervical cancer. 
The CDC recommends the vaccines be delivered in two shots at an interval of least 6 months for those aged 11–12, and three doses for those 13 and older.  In most countries, they are funded only for female use, but are approved for male use in many countries, and funded for teenage boys in Australia. 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. [ citation needed ]
Following studies suggesting that the vaccine is more effective in younger girls  than in older teenagers, the United Kingdom, Switzerland, Mexico, the Netherlands and Quebec began offering the vaccine in a two-dose schedule for girls aged under 15 in 2014. [ citation needed ]
Cervical cancer screening recommendations have not changed for females who receive HPV vaccine. It remains a recommendation that women continue cervical screening, such as Pap smear testing, even after receiving the vaccine, since it does not prevent all types of cervical cancer.  
Both men and women are carriers of HPV.  The Gardasil vaccine also protects men against anal cancers and warts and genital warts. 
Duration of both vaccines' efficacy has been observed since they were first developed, and is expected to be longlasting. 
In December 2014, the FDA approved a nine-valent Gardasil-based vaccine, Gardasil 9, to protect against infection with the four strains of HPV covered by the first generation of Gardasil as well as five other strains responsible for 20% of cervical cancers (HPV-31, HPV-33, HPV-45, HPV-52, and HPV-58). 
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." 
The virus is unusually hardy, and is immune to most common disinfectants. It is the first virus ever shown to be resistant to inactivation by glutaraldehyde, which is among the most common strong disinfectants used in hospitals.  Diluted sodium hypochlorite bleach is effective,  but cannot be used on some types of re-usable equipment, such as ultrasound transducers.  As a result of these difficulties, there is developing concern about the possibility of transmitting the virus on healthcare equipment, particularly reusable gynecological equipment that cannot be autoclaved.   For such equipment, some health authorities encourage use of UV disinfection  or a non-hypochlorite "oxidizing‐based high‐level disinfectant [bleach] with label claims for non‐enveloped viruses",  such as a strong hydrogen peroxide solution   or chlorine dioxide wipes.  Such disinfection methods are expected to be relatively effective against HPV. [ citation needed ]
There is currently no specific treatment for HPV infection.    However, the viral infection is usually cleared to undetectable levels by the immune system.  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.  [ needs update ]
Follow up care is usually recommended and practiced by many health clinics.  Follow-up is sometimes not successful because a portion of those treated do not return to be evaluated. In addition to the normal methods of phone calls and mail, text messaging and email can improve the number of people who return for care.  As of 2015 it is unclear the best method of follow up following treatment of cervical intraepithelial neoplasia. 
Globally, 12% of women are positive for HPV DNA, with rates varying by age and country.  The highest rates of HPV are in younger women, with a rate of 24% in women under 25 years.  Rates decline in older age groups in Europe and the Americas, but less so in Africa and Asia. The rates are highest in Sub-Saharan Africa (24%) and Eastern Europe (21%) and lowest in North America (5%) and Western Asia (2%). 
The most common types of HPV worldwide are HPV16 (3.2%), HPV18 (1.4%), HPV52 (0.9%), HPV31 (0.8%), and HPV58 (0.7%). High-risk types of HPV are also distributed unevenly, with HPV16 having a rate around 13% in Africa and 30% in West and Central Asia. 
Like many diseases, HPV disproportionately affects low-income and resource-poor countries. The higher rates of HPV in Sub-Saharan Africa, for example, may be related to high exposure to human immunodeficiency virus (HIV) in the region. Other factors that impact the global spread of disease are sexual behaviors including age of sexual debut, number of sexual partners, and ease of access to barrier contraception, all of which vary globally.  
United States Edit
|Age (years)||Prevalence (%)|
|14 to 19||24.5%|
|20 to 24||44.8%|
|25 to 29||27.4%|
|30 to 39||27.5%|
|40 to 49||25.2%|
|50 to 59||19.6%|
|14 to 59||26.8%|
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 estimates that about 75–80% 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 15–44 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. [ citation needed ]
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 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.  
On average 538 cases of HPV-associated cancers were diagnosed per year in Ireland during the period 2010 to 2014.  Cervical cancer was the most frequent HPV-associated cancer with on average 292 cases per year (74% of the female total, and 54% of the overall total of HPV-associated cancers).  A study of 996 cervical cytology samples in an Irish urban female, opportunistically screened population, found an overall HPV prevalence of 19.8%, HPV 16 at 20% and HPV 18 at 12% were the commonest high-risk types detected. In Europe, types 16 and 18 are responsible for over 70% of cervical cancers.  Overall rates of HPV-associated invasive cancers may be increasing. Between 1994 and 2014, there was a 2% increase in the rate of HPV-associated invasive cancers per year for both sexes in Ireland. 
As HPV is known to be associated with ano-genital warts, these are notifiable to the Health Protection Surveillance Centre (HPSC). Genital warts are the second most common STI in Ireland.  There were 1,281 cases of ano-genital warts notified in 2017, which was a decrease on the 2016 figure of 1,593.  The highest age-specific rate for both male and female was in the 25-29 year old age range, 53% of cases were among males. 
Sri Lanka Edit
In Sri Lanka, the prevalence of HPV is 15.5% regardless of their cytological abnormalities. 
In 1972, the association of the human papillomaviruses 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 HeLa cell line contains extra DNA in its genome that originated from HPV type 18. 
The Ludwig-McGill HPV Cohort is one of the world's largest longitudinal studies of the natural history of human papillomavirus (HPV) infection and cervical cancer risk. It was established in 1993 by Ludwig Cancer Research and McGill University in Montreal, Canada. [ citation needed ]
T-cells are a type of white blood cell that work with macrophages. Unlike macrophages that can attack any invading cell or virus, each T-cell can fight only one type of virus. You might think this means macrophages are stronger than T-cells, but they aren’t. Instead, T-cells are like a special forces unit that fights only one kind of virus that might be attacking your body.
More than one kind of T-cell
There are two types of T-cells in your body: Helper T-cells and Killer T-cells. Killer T-cells do the work of destroying the infected cells. The Helper T-cells coordinate the attack.
Picture taken with a scanning electron microscope of a T-cell (right), platelet that helps blood to clot (center) and a red blood cell (left). The bumps on the T-cell are T-cell receptors used to fight infections. From The National Cancer Institute.
Killer T-Cells and Antigens
Killer T-cells find and destroy infected cells that have been turned into virus-making factories. To do this they need to tell the difference between the infected cells and healthy cells with the help of special molecules called antigens. Killer T-cells are able to find the cells with viruses and destroy them.
Antigens work like identification tags that give your immune system information about your cells and any intruders. Healthy cells have 'self-antigens' on the surface of their membranes. They let T-cells know that they are not intruders. If a cell is infected with a virus, it has pieces of virus antigens on its surface. This is a signal for the Killer T-cell that lets it know this is a cell that must be destroyed.
The basic anatomy of a T-cell.
Anatomy of a T-cell
T-cells have many identical T-cell receptors that cover their surfaces and can only bind to one shape of antigen. When a T-cell receptor fits with its viral antigen on an infected cell, the Killer T-cell releases cytotoxins to kill that cell.
The key to finding infected cells
There are 25 million to a billion different T-cells in your body. Each cell has a unique T-cell receptor that can fit with only one kind of antigen, like a lock that can fit with only one shape of key. Antigens and receptors work a lot like a lock and key. Most of these antigens will never get in your body, but the T-cells that patrol your body will recognize them if they do.
The T-cell receptor fits with its antigen like a complex key. When the perfectly shaped virus antigen on an infected cell fits into the Killer T-cell receptor, the T-cell releases perforin and cytotoxins. Perforin first makes a pore, or hole, in the membrane of the infected cell. Cytotoxins go directly inside the cell through this pore, destroying it and any viruses inside. This is why Killer T-cells are also called Cytotoxic T-cells. The pieces of destroyed cells and viruses are then cleaned up by macrophages.
The other type of T-cell is the Helper T-cell. These cells don’t make toxins or fight invaders themselves. Instead, they are like team coordinators. They use chemical messages to give instructions to the other immune system cells. These instructions help Killer T-cells and B-cells make a lot more of themselves so they can fight the infection and make sure the fight stays under control.
When a T-cell finds its virus match in your body, it makes many copies of itself to attack that virus.
Building a bigger army for a particular invader
When a Helper T-cell sends out a chemical message, its matched Killer T-cell is alerted that there is a virus present. After a Killer T-cell finds and destroys an infected cell, this Helper T-cell message tells it to copy itself, making an army of Killer T-cells. Because only T-cells that can fight the invading virus are copied, your body saves energy and is still very good at killing the virus.
T-cells are made in the bone marrow, like all red and white blood cells. The name T-cell comes from the organ where they mature, the thymus. The thymus is just above your heart, and is about the size of a deck of playing cards. Most T-cells are made when you’re young, so kids have a bigger thymus than adults. It is also where T-cells are screened to get rid of any that would attack the healthy cells in your body.
Getting around the body
All white blood cells have two ways to get around the body. One way is through your blood vessels. The other way is through the lymph system.
The lymph system has vessels that move milky fluid and white blood cells around the body. Unlike your heart, which pumps your blood, the lymph system uses the movements of your body to push the lymph fluid around. This is one reason why it is good to be active and exercise.
The lymph system moves white blood cells around the body. It includes the lymph nodes, the thymus, spleen, tonsils, and bone marrow, where immune cells grow and multiply.
Switching transportation systems
Most white blood cells are stored in the lymph system until they are needed to fight an infection. When a virus attacks, they can transfer into the blood vessels so they can quickly attack the viruses. This transfer happens in the lymph nodes, which are located throughout your body.
Lots of lymph nodes are in your legs, armpits, and neck. The last time you had a sore throat you probably felt enlarged places on one or both sides of your neck. This is where the T-cells and B-cells multiply and get ready to attack the virus.
Other important parts of the lymph system where immune cells grow, multiply, and trap invaders are your bone marrow, thymus, spleen, and tonsils.