Human Papillomavirus (HPV)- An Overview

Human Papillomavirus (HPV) is a group of more than 100 related viruses that infect the skin or mucosal cells of humans. HPV can cause various benign and malignant lesions, such as warts, cervical cancer, and other anogenital and head and neck cancers.

Structure of HPV

HPV is a small, non-enveloped virus with a diameter of about 52-55 nm. It has an icosahedral capsid composed of 72 pentameric capsomers, each containing five molecules of the major capsid protein L1. The capsid also contains a variable number of molecules of the minor capsid protein L2, which are not fully exposed on the surface of the virion .

The capsid encloses a circular, double-stranded DNA genome of about 8 kb in length. The genome is associated with cellular histones to form nucleosomes.

Genome of HPV

The genome of HPV can be divided into three functional regions: the early region (E), the late region (L), and the long control region (LCR). The E region encodes six proteins (E1-E7) that are involved in viral replication, transcription, and transformation. The L region encodes two proteins (L1 and L2) that are involved in viral assembly and encapsidation. The LCR contains the origin of replication and various cis-regulatory elements that control viral gene expression .

The genome organization of HPV is highly conserved among different types, but there is considerable variation in the nucleotide sequence and gene expression patterns. HPV types are classified into low-risk and high-risk groups based on their association with cervical cancer and other malignancies. Low-risk types (such as HPV 6 and 11) mainly cause benign lesions, such as genital warts, while high-risk types (such as HPV 16 and 18) can cause precancerous and cancerous lesions of the cervix and other anogenital and oropharyngeal sites .

• HPV is a group of more than 180 subtypes of non-enveloped, double-stranded, circular DNA viruses that infect cutaneous or mucosal epithelial cells and cause various benign or malignant lesions.
• HPV subtypes show a predilection for body sites they most commonly infect, and disease manifestations that result from infection may vary.
• Cutaneous warts of the hands and feet, such as verruca vulgaris or verruca plantaris, are most commonly caused by HPV subtypes 1, 2, 4, 27, or 57. These are spread through contact between skin with epidermal damage or through infected fomites.
• HPV subtypes 6 and 11 are generally associated with anogenital warts, such as condyloma acuminatum. They are termed low-risk HPV and are also associated with juvenile and adult recurrent respiratory papillomatosis.
• Subtypes 16 and 18 most commonly cause pre-cancerous and cancerous lesions of the cervix, male and female anogenital areas, and oropharyngeal area. They are termed high-risk HPV and account for about 70% of cervical cancer cases worldwide.
• Subtypes 31, 33, 35, 45, 52, and 58 also belong to the high-risk HPV and are associated with cervical cancer development. They account for about 20% of cervical cancer cases worldwide.
• Although both the low-risk and high-risk HPV are considered sexually transmitted agents, they can also transmit through other forms of close contact.
• According to the World Health Organization (WHO), HPV is the most common viral infection of the reproductive tract. It affects both men and women globally. More than 80% of sexually active women will have an HPV infection at some point in their lives.
• The global prevalence of HPV infection among women with normal cytology is estimated to be 11.7%, with regional variations ranging from 5.2% in North America to 24% in Africa.
• The global prevalence of HPV infection among women with cervical cancer is estimated to be 85.6%, with regional variations ranging from 74.7% in Europe to 88.8% in Africa.
• The global burden of cervical cancer is estimated to be 570,000 new cases and 311,000 deaths in 2018. More than 85% of these cases and deaths occur in low- and middle-income countries.
• The global burden of other HPV-related cancers is estimated to be 120,000 new cases and 50,000 deaths in men and women combined in 2018. These include cancers of the vulva, vagina, penis, anus, and oropharynx.

Different subtypes of HPV affect the mouth, throat, or genital area. Although it a common STD, it can be asymptomatic and resolve on its own. Penetrative sex is not required for the spread of the virus. It can transmit through:

• Skin-to-skin contact of the genital area
• Vaginal, anal, or oral sex
• Sharing of sex toys

Some of the risk factors for acquiring HPV infection include:

• Sexual activity, age of first sexual intercourse, and number of sexual partners
• Smoking
• Use of oral contraceptives (for more than 5 years)
• Chewing betel nut
• Exposure to radiation and UV light

• Having a compromised immune system, such as from HIV or drugs from an organ transplant

  Replication process of HPV

HPV infects the epithelial cells of the skin or mucosa and replicates its DNA in a manner that is closely linked to the differentiation of the host cells. The HPV replication cycle can be divided into three phases: initial amplification, maintenance, and productive amplification.

Initial amplification

• This phase occurs in the basal layer of the epithelium, where HPV enters through microabrasions or wounds.
• The viral capsid protein L1 binds to heparan sulfate proteoglycans (HSPGs) on the cell surface and mediates endocytosis of the virus.
• The viral DNA is released into the cytoplasm and transported to the nucleus by microtubules or during mitosis.
• The viral DNA exists as a circular episome that associates with cellular histones and other proteins.
• The viral early promoter is activated by cellular transcription factors and drives the expression of viral early genes E1, E2, E6, and E7.
• E1 and E2 are essential for viral DNA replication. E1 is a helicase that unwinds the DNA and recruits cellular DNA polymerase. E2 is a transcription factor that binds to the viral origin of replication (ori) and regulates E1 activity and viral gene expression.
• E6 and E7 are oncogenes that modulate the cell cycle and inhibit apoptosis. E6 degrades p53, a tumor suppressor protein that induces cell cycle arrest and DNA repair. E7 binds to and inactivates retinoblastoma protein (Rb), a regulator of cell cycle progression and transcription.
• The initial amplification produces 50 to 100 copies of viral DNA per cell, which are distributed to daughter cells upon cell division.

Maintenance

• This phase occurs in the suprabasal layer of the epithelium, where HPV-infected cells undergo differentiation.
• The viral DNA replication switches from a continuous mode to a once-per-cell-cycle mode, which ensures stable maintenance of the episomes at low copy numbers (10 to 50 per cell).
• The viral early promoter is repressed by cellular differentiation factors and by E2 itself, which reduces the expression of E1, E2, E6, and E7.
• The viral DNA replication is regulated by cellular replication factors that are activated during the S phase of the cell cycle.
• The maintenance phase can last for months or years without producing infectious virions or causing symptoms.

Productive amplification

• This phase occurs in the upper differentiated layer of the epithelium, where HPV completes its life cycle and produces progeny virions.
• The viral late promoter is activated by cellular differentiation factors and drives the expression of viral late genes L1 and L2, which encode the capsid proteins.
• The viral DNA replication switches from a once-per-cell-cycle mode to a continuous mode, which results in thousands of copies of viral DNA per cell.
• The viral DNA replication uses a rolling circle mechanism that generates concatemeric intermediates that are cleaved into unit-length genomes by cellular or viral enzymes.
• The viral genomes are encapsidated by L1 and L2 proteins in the nucleus, forming infectious virions that are released upon cell death or desquamation.

Pathogenesis and Clinical Manifestations of HPV

Although having high prevalence rates, HPV infections usually resolve spontaneously within a year or two. The persistence of the infection is an important contributor to the development of cervical and other cancers.

HPVs infect cutaneous or mucosal epithelial cells and initiate benign or cancerous lesions depending on the HPV type. As the host immune response mechanisms play a significant role in controlling the HPV infection, its prevalence is seen higher in immunocompromised individuals. Once the virus infects the target cells, it does not lyse the cell or cause viremia that reduces the exposure of viral antigen that aids to evade the host immune response.

The HPV also has the ability to downregulate major histocompatibility complex class I (MHC 1) and disrupt the interferon (IFN) pathway facilitated by oncoproteins E5, E6, and E7. HLA molecules and intracellular viral antigenic peptides complex are transported through the Golgi apparatus and to the cell surface where they get recognized by the cytotoxic CD8+ T cells. The activated cytotoxic T lymphocytes (CTLs) then cause the apoptosis of the infected cells. The T helper cells secrete cytokines that allow proliferation, maintenance of cytotoxic lymphocytes, and activation of B cells for antibody production.

HR-HPV types are generally associated with many types of cancers like cervical cancer and hence the presence of certain genotypes indicates a risk factor for initiation and progression of 90% of cervical cancer cases.

Most HPV infections are asymptomatic where the infection resolves without knowledge of the patient acquiring the virus. About 90% of the patients with high-risk or low-risk HPV are cleared of the infection within two years. The clinical symptoms of the HPV include:

• Mucosal human papillomavirus infections:
  • Condyloma acuminatum (Present as papules, nodules, or soft, filiform, pinkish, sessile, or pedunculated growths in the genital area)
  • Focal epithelial hyperplasia (disease of the oral mucosa more common in children and women)
  • Cervical neoplasia and cervical cancer
  • Other anogenital cancers (including those of the vulva, vagina, penis, and anus)
  • Head and neck cancer
• Cutaneous human papillomavirus infections:
  • Common warts
  • Plantar warts
  • Flat warts
  • Filiform warts
  • Pigmented warts
  • Epidermal cysts
  • Skin cancer (Bowen’s disease)

Diagnosis methods for HPV detection

There are different methods for diagnosing HPV infection depending on the type and location of the infection, the clinical manifestations, and the purpose of the test. Some of the common methods are:

• Warts/Condyloma detection: This method involves visual inspection of the genital or oral warts by looking at their shape, color, size, and texture. Sometimes, a biopsy may be needed to confirm the diagnosis and rule out other conditions.
• Colposcopy and acetic acid test: This method is used for examining the cervix, vagina, and vulva for abnormal lesions that may be caused by HPV. A solution of acetic acid (vinegar) is applied to the genital area, which turns the HPV-infected areas white. A colposcope, a magnifying instrument with a light source, is then used to view the cervix and take biopsies if needed. The biopsies are then examined under a microscope for signs of dysplasia or cancer.
• Pap test: This method is used for screening cervical cancer and precancerous lesions in women. It involves scraping cells from the cervix and examining them under a microscope for abnormalities. The Pap test can also detect some types of HPV infection, but it cannot identify the specific type or determine the risk of cancer.
• HPV test: This method is used to detect the presence and type of HPV DNA in cervical cells. It can be done along with the Pap test or separately. The HPV test can identify high-risk types of HPV that are associated with cervical cancer, such as HPV-16 and HPV-18. It can also detect low-risk types that cause genital warts, such as HPV-6 and HPV-11. The HPV test can help determine the need for further testing or treatment in women who have abnormal Pap results or who are at high risk of cervical cancer.
• HPV genotyping detection kit: This method is used to identify the specific type of HPV infection in cervical samples. It can detect up to 14 high-risk types of HPV and 5 low-risk types using polymerase chain reaction (PCR) technology. It can help guide clinical management and prevention strategies for women who are infected with HPV.

Treatment options for HPV infection

There is no specific treatment for the HPV virus itself, but there are treatments for the health problems that HPV can cause, such as genital warts, cervical precancer, and other HPV-related cancers. The type and location of HPV infection determine the appropriate treatment option.

Genital warts

Genital warts are caused by low-risk HPV types, such as 6 and 11. They appear as soft, flesh-colored growths on the genital area or anus. They may be flat or raised, single or multiple, small or large. They are usually painless but may cause itching, bleeding, or discomfort.

Genital warts can be treated by a healthcare provider or with prescription medication. Some of the common treatment options include :

• Freezing (cryotherapy): This involves applying liquid nitrogen to the warts to destroy the abnormal tissue. The procedure may cause mild pain and blistering. It may require several sessions to clear the warts completely.
• Burning (electrocautery): This involves using an electric current to burn off the warts. The procedure may cause pain and scarring. It may require local anesthesia and a single session to remove the warts.
• Surgical removal (excision): This involves cutting off the warts with a scalpel or scissors. The procedure may cause pain and bleeding. It may require local anesthesia and stitches to close the wound.
• Laser surgery: This involves using a high-intensity light beam to vaporize the warts. The procedure may cause pain and scarring. It may require general anesthesia and a single session to remove the warts.

• Topical medications: These include creams or solutions that are applied to the warts to destroy or stimulate the immune system to fight them. Some of the common topical medications are:

  • Imiquimod: This is an immune response modifier that boosts the body`s natural defense against HPV. It is applied three times a week at bedtime and washed off after 6 to 10 hours. It may cause redness, itching, burning, or swelling at the application site. It may take several weeks to months to clear the warts completely.
  • Podophyllin: This is a plant extract that contains antiviral and anti-tumor properties. It is applied by a healthcare provider once a week and washed off after 4 hours. It may cause skin irritation, ulceration, or systemic toxicity if absorbed into the bloodstream. It should not be used by pregnant women or people with kidney or liver problems.
  • Trichloroacetic acid: This is a chemical agent that burns off the warts. It is applied by a healthcare provider once a week and washed off after a few minutes. It may cause skin irritation, blistering, or scarring.
  • Sinecatechins: This is an extract from green tea leaves that has anti-inflammatory and antioxidant effects. It is applied three times a day for up to 16 weeks. It may cause redness, itching, burning, or pain at the application site.

If left untreated, genital warts may go away, stay the same, or grow in size or number. Treatment does not eliminate the HPV infection from the body and does not prevent transmission to others. Therefore, it is important to use condoms and/or dental dams during sexual activity to reduce the risk of spreading HPV.

Cervical precancer

Cervical precancer is caused by high-risk HPV types, such as 16 and 18. It refers to abnormal changes in the cells of the cervix that can progress to cervical cancer if left untreated. Cervical precancer can be detected by routine Pap tests and HPV tests that collect samples of cervical cells for laboratory analysis. If abnormal cells are found, a procedure called colposcopy is used to examine and biopsy any suspicious areas on the cervix. Depending on the severity of the precancerous lesions, one of the following treatments may be recommended :

• Freezing (cryosurgery): This involves using a metal probe cooled with liquid nitrogen to freeze and destroy the abnormal tissue on the cervix. The procedure may cause mild cramping, bleeding, or discharge. It can be done in an outpatient setting with local anesthesia.
• Laser: This involves using a high-intensity light beam to vaporize the abnormal tissue on the cervix. The procedure may cause mild cramping, bleeding, or discharge. It can be done in an outpatient setting with local anesthesia.
• Surgical removal (conization): This involves cutting out a cone-shaped piece of tissue from the cervix that contains the abnormal cells. The procedure may cause bleeding, infection, or cervical stenosis (narrowing of the cervix). It can be done in an outpatient setting with local anesthesia.
• Loop electrosurgical excision procedure (LEEP): This involves using a thin wire loop heated by an electric current to cut out the abnormal tissue on the cervix. The procedure may cause mild cramping, bleeding, or discharge. It can be done in an outpatient setting with local anesthesia.

Treatment for cervical precancer can cure most cases and prevent cervical cancer from developing. However, treatment does not eliminate the HPV infection from the body and does not prevent recurrence of precancerous lesions. Therefore, it is important to have regular follow-up Pap tests and HPV tests to monitor any changes in cervical cells.

Other HPV-related cancers

Other HPV-related cancers include those of the vulva, vagina, penis, anus, and oropharynx (mouth and throat). These cancers are also caused by high-risk HPV types

Vaccination and prevention measures for HPV

One of the most effective ways to prevent HPV infection and its associated cancers is vaccination. HPV vaccines are safe, effective, and long-lasting. They can protect against the most common and harmful types of HPV that cause cervical, anogenital, and oropharyngeal cancers, as well as genital warts.

Who should get HPV vaccine?

The Centers for Disease Control and Prevention (CDC) recommends that HPV vaccine be given to both boys and girls at ages 11–12 years . HPV vaccines can be given starting at age 9 years. The vaccine works best when given before exposure to HPV through sexual activity .

Teens and young adults through age 26 years who did not start or finish the HPV vaccine series also need HPV vaccination . CDC recommends that 11- to 12-year-olds receive two doses of HPV vaccine 6 to 12 months apart . Only two doses are needed if the first dose was given before the 15th birthday . Teens and young adults who start the series later, at ages 15 through 26 years, need three doses of HPV vaccine .

Some adults age 27 through 45 years who are not already vaccinated may decide to get HPV vaccine after speaking with their doctor about their risk for new HPV infections and the possible benefits of vaccination for them . However, HPV vaccination in this age range provides less benefit, because more people in this age range have already been exposed to HPV .

People with weakened immune systems or certain health conditions may also need HPV vaccination. They should talk to their doctor about their specific recommendations .

Who should not get HPV vaccine?

Some people should not get some HPV vaccines if:

• They have ever had a life-threatening allergic reaction to any ingredient of an HPV vaccine, or to a previous dose of HPV vaccine .
• They have an allergy to yeast (Gardasil and Gardasil 9) .
• They are pregnant .

People with a moderate or severe illness should wait until they are better before getting vaccinated .

What types of HPV vaccines are there?

Three HPV vaccines—9-valent HPV vaccine (Gardasil 9, 9vHPV), quadrivalent HPV vaccine (Gardasil, 4vHPV), and bivalent HPV vaccine (Cervarix, 2vHPV)—have been licensed by the U.S. Food and Drug Administration (FDA) . All three HPV vaccines protect against HPV types 16 and 18 that cause most HPV cancers . Since late 2016, only Gardasil-9 (9vHPV) is distributed in the United States . This vaccine protects against nine HPV types (6, 11, 16, 18, 31, 33, 45, 52, and 58) .

How well do these vaccines work?

HPV vaccination works extremely well. HPV vaccine has the potential to prevent more than 90% of HPV-attributable cancers. Since HPV vaccination was first recommended in 2006, infections with HPV types that cause most HPV cancers and genital warts have dropped significantly among teen girls and young adult women. Fewer teens and young adults are getting genital warts. HPV vaccination has also reduced the number of cases of precancers of the cervix in young women.

How can I get vaccinated?

You can get vaccinated at your doctor`s office or clinic. You may also find a nearby location that offers the vaccine by using the Vaccine Finder tool on the CDC website. Most health insurance plans cover the cost of recommended vaccines. If you do not have health insurance or your plan does not cover vaccines, you may be eligible for free or low-cost vaccines through the Vaccines for Children Program or other programs in your state or local area.

What else can I do to prevent HPV infection?

Besides getting vaccinated, you can also lower your risk of getting or spreading HPV by:

• Using condoms and/or dental dams during vaginal, anal, or oral sex.
• Limiting your number of sexual partners.
• Getting regular screening tests for cervical cancer if you are a woman aged 21 to 65 years.
• Avoiding smoking and chewing betel nut.
• Seeking medical attention if you notice any symptoms or signs of HPV infection or related cancers.

Although having high prevalence rates, HPV infections usually resolve spontaneously within a year or two. The persistence of the infection is an important contributor to the development of cervical and other cancers.

HPVs infect cutaneous or mucosal epithelial cells and initiate benign or cancerous lesions depending on the HPV type. As the host immune response mechanisms play a significant role in controlling the HPV infection, its prevalence is seen higher in immunocompromised individuals. Once the virus infects the target cells, it does not lyse the cell or cause viremia that reduces the exposure of viral antigen that aids to evade the host immune response.

The HPV also has the ability to downregulate major histocompatibility complex class I (MHC 1) and disrupt the interferon (IFN) pathway facilitated by oncoproteins E5, E6, and E7. HLA molecules and intracellular viral antigenic peptides complex are transported through the Golgi apparatus and to the cell surface where they get recognized by the cytotoxic CD8+ T cells. The activated cytotoxic T lymphocytes (CTLs) then cause the apoptosis of the infected cells. The T helper cells secrete cytokines that allow proliferation, maintenance of cytotoxic lymphocytes, and activation of B cells for antibody production.

HR-HPV types are generally associated with many types of cancers like cervical cancer and hence the presence of certain genotypes indicates a risk factor for initiation and progression of 90% of cervical cancer cases.

Most HPV infections are asymptomatic where the infection resolves without knowledge of the patient acquiring the virus. About 90% of the patients with high-risk or low-risk HPV are cleared of the infection within two years. The clinical symptoms of the HPV include:

• Mucosal human papillomavirus infections:
  • Condyloma acuminatum (Present as papules, nodules, or soft, filiform, pinkish, sessile, or pedunculated growths in the genital area)
  • Focal epithelial hyperplasia (disease of the oral mucosa more common in children and women)
  • Cervical neoplasia and cervical cancer
  • Other anogenital cancers (including those of the vulva, vagina, penis, and anus)
  • Head and neck cancer
• Cutaneous human papillomavirus infections:
  • Common warts
  • Plantar warts
  • Flat warts
  • Filiform warts
  • Pigmented warts
  • Epidermal cysts
  • Skin cancer (Bowen’s disease)

There are different methods for diagnosing HPV infection depending on the type and location of the infection, the clinical manifestations, and the purpose of the test. Some of the common methods are:

• Warts/Condyloma detection: This method involves visual inspection of the genital or oral warts by looking at their shape, color, size, and texture. Sometimes, a biopsy may be needed to confirm the diagnosis and rule out other conditions.
• Colposcopy and acetic acid test: This method is used for examining the cervix, vagina, and vulva for abnormal lesions that may be caused by HPV. A solution of acetic acid (vinegar) is applied to the genital area, which turns the HPV-infected areas white. A colposcope, a magnifying instrument with a light source, is then used to view the cervix and take biopsies if needed. The biopsies are then examined under a microscope for signs of dysplasia or cancer.
• Pap test: This method is used for screening cervical cancer and precancerous lesions in women. It involves scraping cells from the cervix and examining them under a microscope for abnormalities. The Pap test can also detect some types of HPV infection, but it cannot identify the specific type or determine the risk of cancer.
• HPV test: This method is used to detect the presence and type of HPV DNA in cervical cells. It can be done along with the Pap test or separately. The HPV test can identify high-risk types of HPV that are associated with cervical cancer, such as HPV-16 and HPV-18. It can also detect low-risk types that cause genital warts, such as HPV-6 and HPV-11. The HPV test can help determine the need for further testing or treatment in women who have abnormal Pap results or who are at high risk of cervical cancer.
• HPV genotyping detection kit: This method is used to identify the specific type of HPV infection in cervical samples. It can detect up to 14 high-risk types of HPV and 5 low-risk types using polymerase chain reaction (PCR) technology. It can help guide clinical management and prevention strategies for women who are infected with HPV.

There is no specific treatment for the HPV virus itself, but there are treatments for the health problems that HPV can cause, such as genital warts, cervical precancer, and other HPV-related cancers. The type and location of HPV infection determine the appropriate treatment option.

Genital warts

Genital warts are caused by low-risk HPV types, such as 6 and 11. They appear as soft, flesh-colored growths on the genital area or anus. They may be flat or raised, single or multiple, small or large. They are usually painless but may cause itching, bleeding, or discomfort.

Genital warts can be treated by a healthcare provider or with prescription medication. Some of the common treatment options include :

• Freezing (cryotherapy): This involves applying liquid nitrogen to the warts to destroy the abnormal tissue. The procedure may cause mild pain and blistering. It may require several sessions to clear the warts completely.
• Burning (electrocautery): This involves using an electric current to burn off the warts. The procedure may cause pain and scarring. It may require local anesthesia and a single session to remove the warts.
• Surgical removal (excision): This involves cutting off the warts with a scalpel or scissors. The procedure may cause pain and bleeding. It may require local anesthesia and stitches to close the wound.
• Laser surgery: This involves using a high-intensity light beam to vaporize the warts. The procedure may cause pain and scarring. It may require general anesthesia and a single session to remove the warts.

• Topical medications: These include creams or solutions that are applied to the warts to destroy or stimulate the immune system to fight them. Some of the common topical medications are:

  • Imiquimod: This is an immune response modifier that boosts the body`s natural defense against HPV. It is applied three times a week at bedtime and washed off after 6 to 10 hours. It may cause redness, itching, burning, or swelling at the application site. It may take several weeks to months to clear the warts completely.
  • Podophyllin: This is a plant extract that contains antiviral and anti-tumor properties. It is applied by a healthcare provider once a week and washed off after 4 hours. It may cause skin irritation, ulceration, or systemic toxicity if absorbed into the bloodstream. It should not be used by pregnant women or people with kidney or liver problems.
  • Trichloroacetic acid: This is a chemical agent that burns off the warts. It is applied by a healthcare provider once a week and washed off after a few minutes. It may cause skin irritation, blistering, or scarring.
  • Sinecatechins: This is an extract from green tea leaves that has anti-inflammatory and antioxidant effects. It is applied three times a day for up to 16 weeks. It may cause redness, itching, burning, or pain at the application site.

If left untreated, genital warts may go away, stay the same, or grow in size or number. Treatment does not eliminate the HPV infection from the body and does not prevent transmission to others. Therefore, it is important to use condoms and/or dental dams during sexual activity to reduce the risk of spreading HPV.

Cervical precancer

Cervical precancer is caused by high-risk HPV types, such as 16 and 18. It refers to abnormal changes in the cells of the cervix that can progress to cervical cancer if left untreated. Cervical precancer can be detected by routine Pap tests and HPV tests that collect samples of cervical cells for laboratory analysis. If abnormal cells are found, a procedure called colposcopy is used to examine and biopsy any suspicious areas on the cervix. Depending on the severity of the precancerous lesions, one of the following treatments may be recommended :

• Freezing (cryosurgery): This involves using a metal probe cooled with liquid nitrogen to freeze and destroy the abnormal tissue on the cervix. The procedure may cause mild cramping, bleeding, or discharge. It can be done in an outpatient setting with local anesthesia.
• Laser: This involves using a high-intensity light beam to vaporize the abnormal tissue on the cervix. The procedure may cause mild cramping, bleeding, or discharge. It can be done in an outpatient setting with local anesthesia.
• Surgical removal (conization): This involves cutting out a cone-shaped piece of tissue from the cervix that contains the abnormal cells. The procedure may cause bleeding, infection, or cervical stenosis (narrowing of the cervix). It can be done in an outpatient setting with local anesthesia.
• Loop electrosurgical excision procedure (LEEP): This involves using a thin wire loop heated by an electric current to cut out the abnormal tissue on the cervix. The procedure may cause mild cramping, bleeding, or discharge. It can be done in an outpatient setting with local anesthesia.

Treatment for cervical precancer can cure most cases and prevent cervical cancer from developing. However, treatment does not eliminate the HPV infection from the body and does not prevent recurrence of precancerous lesions. Therefore, it is important to have regular follow-up Pap tests and HPV tests to monitor any changes in cervical cells.

Other HPV-related cancers

Other HPV-related cancers include those of the vulva, vagina, penis, anus, and oropharynx (mouth and throat). These cancers are also caused by high-risk HPV types

One of the most effective ways to prevent HPV infection and its associated cancers is vaccination. HPV vaccines are safe, effective, and long-lasting. They can protect against the most common and harmful types of HPV that cause cervical, anogenital, and oropharyngeal cancers, as well as genital warts.

Who should get HPV vaccine?

The Centers for Disease Control and Prevention (CDC) recommends that HPV vaccine be given to both boys and girls at ages 11–12 years . HPV vaccines can be given starting at age 9 years. The vaccine works best when given before exposure to HPV through sexual activity .

Teens and young adults through age 26 years who did not start or finish the HPV vaccine series also need HPV vaccination . CDC recommends that 11- to 12-year-olds receive two doses of HPV vaccine 6 to 12 months apart . Only two doses are needed if the first dose was given before the 15th birthday . Teens and young adults who start the series later, at ages 15 through 26 years, need three doses of HPV vaccine .

Some adults age 27 through 45 years who are not already vaccinated may decide to get HPV vaccine after speaking with their doctor about their risk for new HPV infections and the possible benefits of vaccination for them . However, HPV vaccination in this age range provides less benefit, because more people in this age range have already been exposed to HPV .

People with weakened immune systems or certain health conditions may also need HPV vaccination. They should talk to their doctor about their specific recommendations .

Who should not get HPV vaccine?

Some people should not get some HPV vaccines if:

• They have ever had a life-threatening allergic reaction to any ingredient of an HPV vaccine, or to a previous dose of HPV vaccine .
• They have an allergy to yeast (Gardasil and Gardasil 9) .
• They are pregnant .

People with a moderate or severe illness should wait until they are better before getting vaccinated .

What types of HPV vaccines are there?

Three HPV vaccines—9-valent HPV vaccine (Gardasil 9, 9vHPV), quadrivalent HPV vaccine (Gardasil, 4vHPV), and bivalent HPV vaccine (Cervarix, 2vHPV)—have been licensed by the U.S. Food and Drug Administration (FDA) . All three HPV vaccines protect against HPV types 16 and 18 that cause most HPV cancers . Since late 2016, only Gardasil-9 (9vHPV) is distributed in the United States . This vaccine protects against nine HPV types (6, 11, 16, 18, 31, 33, 45, 52, and 58) .

How well do these vaccines work?

HPV vaccination works extremely well. HPV vaccine has the potential to prevent more than 90% of HPV-attributable cancers. Since HPV vaccination was first recommended in 2006, infections with HPV types that cause most HPV cancers and genital warts have dropped significantly among teen girls and young adult women. Fewer teens and young adults are getting genital warts. HPV vaccination has also reduced the number of cases of precancers of the cervix in young women.

How can I get vaccinated?

You can get vaccinated at your doctor`s office or clinic. You may also find a nearby location that offers the vaccine by using the Vaccine Finder tool on the CDC website. Most health insurance plans cover the cost of recommended vaccines. If you do not have health insurance or your plan does not cover vaccines, you may be eligible for free or low-cost vaccines through the Vaccines for Children Program or other programs in your state or local area.

What else can I do to prevent HPV infection?

Besides getting vaccinated, you can also lower your risk of getting or spreading HPV by:

• Using condoms and/or dental dams during vaginal, anal, or oral sex.
• Limiting your number of sexual partners.
• Getting regular screening tests for cervical cancer if you are a woman aged 21 to 65 years.
• Avoiding smoking and chewing betel nut.
• Seeking medical attention if you notice any symptoms or signs of HPV infection or related cancers.

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