Cervical cancer is one of the most common cancers among women in Thailand and worldwide. According to the World Health Organization (WHO), approximately 99% of cervical cancer cases are associated with persistent infection by high-risk types of the human papillomavirus (HPV). HPV is also a major cause of anal cancer, vaginal cancer, vulvar cancer, and certain cancers of the head and neck in both women and men.
One of the greatest concerns about HPV is that most infected individuals have no symptoms, allowing the virus to be unknowingly transmitted to others. For this reason, prevention is more effective than treatment. Today, HPV vaccination is considered one of the most important strategies for reducing the risk of HPV-related diseases at both the individual and population levels.
This article provides a comprehensive overview of HPV, including the nature of the virus, the differences between the 4-valent and 9-valent HPV vaccines, who should receive vaccination, the recommended number of doses by age, how to prepare before vaccination, and the possible side effects to be aware of.
What Causes Cervical Cancer and Anal Cancer?
What Is HPV?
Human papillomavirus (HPV) is a virus transmitted through close skin-to-skin and mucosal contact, particularly during sexual activity, including vaginal, oral, and anal sex. HPV is a highly diverse group of viruses, with more than 200 identified types. These are broadly classified into two categories according to their cancer-causing potential.
Low-risk HPV types, including HPV 6 and HPV 11, are primarily associated with genital warts and have a very low likelihood of progressing to cancer.
High-risk HPV types, including HPV 16, 18, 31, 33, 45, 52, 58, and several others, are associated with cervical cancer, anal cancer, vaginal cancer, vulvar cancer, and certain cancers of the head and neck.
According to the International Agency for Research on Cancer (IARC), HPV 16 and HPV 18 account for approximately 70% of cervical cancer cases worldwide. When five additional high-risk types (31, 33, 45, 52, and 58) are included, this proportion increases to approximately 85–90%.
How Is HPV Transmitted?
HPV spreads from person to person through direct contact with infected skin or mucous membranes. The most common route of transmission is sexual contact of any kind. Having multiple sexual partners increases the likelihood of exposure to different HPV types. HPV can also be transmitted even without penetrative intercourse, as direct genital skin-to-skin contact alone may be sufficient for infection.
One of the reasons HPV is particularly concerning is that most infected individuals have no symptoms and are unaware they carry the virus. As a result, they may unknowingly transmit HPV to their sexual partners. Although condoms can reduce the risk of transmission, they do not provide complete protection because the virus may infect areas of skin that are not covered by a condom.
Caused by Persistent Infection with High-Risk HPV Types
Most cases of cervical cancer and anal cancer are linked to persistent infection with high-risk HPV types, particularly HPV 16 and HPV 18, as well as other high-risk types such as HPV 31, 33, 45, 52, and 58. The progression from HPV infection to cancer usually takes many years or even decades, beginning with precancerous cellular changes (dysplasia) before developing into early-stage and eventually invasive cancer.
According to the U.S. National Cancer Institute (NCI), HPV is associated with approximately 90% of anal cancers, 70% of vaginal cancers, and 60% of vulvar cancers.
Does HPV Infection Always Lead to Cancer?
HPV infection does not mean that a person will inevitably develop cancer. In most individuals with a healthy immune system, the body clears HPV naturally within one to two years after infection.
However, when infection with a high-risk HPV type persists over a long period, the risk of developing precancerous changes and cancer increases significantly. Factors that further increase this risk include weakened immunity, cigarette smoking, having multiple sexual partners, and a history of other sexually transmitted infections.
Most HPV Infections Do Not Cause Symptoms
Most people infected with HPV do not develop obvious symptoms, particularly those infected with high-risk HPV types associated with cancer. These high-risk strains usually cause no noticeable signs during the early stages of infection. Abnormal changes are typically detected only through cervical cancer screening, such as a Pap smear or an HPV DNA test. This is one of the main reasons why routine cervical cancer screening remains important, even for individuals who have already received the HPV vaccine.
The differences in symptoms are not determined by whether the vaccine protects against 4 or 9 HPV types. Instead, they depend on the specific HPV type involved and whether it belongs to the low-risk or high-risk group.
HPV Types 6 and 11 Are Commonly Associated with Genital Warts
HPV types 6 and 11 are classified as low-risk types and are included in both the 4-valent and 9-valent HPV vaccines. These two types are the primary cause of genital warts (condyloma acuminata), which typically appear as raised bumps, fleshy growths, or small wart-like lesions around the genital area, anus, or nearby mucosal tissues.
Although genital warts can be treated, they may recur and can have a significant impact on a person’s quality of life and emotional well-being. In addition, HPV types 6 and 11 are associated with recurrent respiratory papillomatosis (RRP), a condition characterized by the growth of benign tumors within the respiratory tract.
HPV Types 16, 18, 31, 33, 45, 52, and 58 Usually Cause No Early Symptoms
These high-risk HPV types generally do not produce visible or noticeable symptoms during the early stages of infection. Individuals infected with these strains may continue their normal daily lives without realizing they carry the virus. If the infection persists for many years, abnormal cellular changes may gradually develop in the cervix or anal canal. These changes can only be detected through appropriate screening tests and cannot be recognized by symptoms or self-examination alone.
What Is the HPV Vaccine?
What Does the HPV Vaccine Protect Against?
The HPV vaccine is a recombinant vaccine produced from HPV virus-like particles (VLPs), which are made from the virus’s outer protein shell. Because the vaccine does not contain the virus’s genetic material, it cannot cause HPV infection. Once vaccinated, the immune system produces protective antibodies that can respond rapidly if the body is exposed to HPV in the future.
The HPV vaccine helps protect against several HPV-related diseases and conditions, including:
- Cervical cancer, primarily caused by high-risk HPV types
- Anal cancer in both women and men
- Vaginal cancer and vulvar cancer
- Certain HPV-related cancers of the head and neck
- Genital warts caused by HPV types 6 and 11 (in vaccines that include these two types)
A clinical study published in the New England Journal of Medicine by Joura et al. (2015) reported that the 9-valent HPV vaccine demonstrated approximately 97% efficacy in preventing lesions associated with the HPV types included in the vaccine among individuals who had not previously been infected.
Can the HPV Vaccine Treat Existing HPV Infection?
The HPV vaccine is designed to prevent infection, not to treat it. It has no effect on HPV infections that are already present in the body and cannot eliminate the virus or treat existing HPV-related conditions, including genital warts, abnormal cervical cells, or HPV-associated cancers.
For this reason, vaccination provides the greatest benefit when administered before exposure to HPV. However, individuals who are already sexually active or who have previously tested positive for certain HPV types may still benefit from vaccination because it can protect against other HPV types to which they have not yet been exposed. A healthcare provider should assess each case individually to determine the potential benefits of vaccination.
What Is the 4-Valent HPV Vaccine?
The 4-valent HPV vaccine (Quadrivalent HPV Vaccine) protects against four HPV types: HPV 6, 11, 16, and 18. HPV 16 and HPV 18 are the two major high-risk types responsible for most cases of cervical cancer, anal cancer, and other HPV-related cancers, while HPV 6 and HPV 11 are primarily associated with genital warts.
A study by Villa et al., published in The Lancet Oncology (2005), demonstrated that the 4-valent vaccine was highly effective in preventing lesions associated with HPV types 6, 11, 16, and 18 among women who had not previously been infected with these HPV types.
What Is the 9-Valent HPV Vaccine?
The 9-valent HPV vaccine (Gardasil 9) protects against nine HPV types: HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58. It includes all four HPV types covered by the quadrivalent vaccine while adding five additional high-risk types: HPV 31, 33, 45, 52, and 58.
The 9-valent HPV vaccine was approved by the U.S. Food and Drug Administration (FDA) in 2014. It is currently the HPV vaccine preferentially recommended by the Advisory Committee on Immunization Practices (ACIP) for routine use in the United States.
How Does the 9-Valent Vaccine Provide Broader Protection?
The 9-valent vaccine expands protection by covering five additional high-risk HPV types (31, 33, 45, 52, and 58). Together, these types account for approximately 15–20% of cervical cancers and other HPV-related cancers beyond those caused by HPV 16 and 18.
According to the European Centre for Disease Prevention and Control (ECDC), the 9-valent vaccine offers substantially broader coverage against cancer-causing HPV types than the 4-valent vaccine. Overall, the nine HPV types included in the vaccine are responsible for approximately 85–90% of cervical cancer cases worldwide.
Comparison of the 4-Valent and 9-Valent HPV Vaccines
Comparison of HPV Types Covered and Key Features
| Feature | 4-Valent HPV Vaccine | 9-Valent HPV Vaccine |
|---|---|---|
| Brand name | Gardasil (original formulation) | Gardasil 9 |
| HPV types covered | 6, 11, 16, 18 | 6, 11, 16, 18, 31, 33, 45, 52, 58 |
| Protection against genital warts | ✓ (HPV 6, 11) | ✓ (HPV 6, 11) |
| Protection against cervical cancer | ✓ (~70%) | ✓ (~85-90%) |
| Protection against anal cancer | ✓ | ✓ (broader coverage) |
| Recommended doses | 2-3 doses (depending on age) | 2-3 doses (depending on age) |
| Additional high-risk HPV types | – | HPV 31, 33, 45, 52, 58 |
| Current ACIP recommendation | ✓ | ✓ (preferred option) |
Summary of the Differences Between the 4-Valent and 9-Valent HPV Vaccines
The 4-valent HPV vaccine protects against the major HPV types responsible for cervical cancer and genital warts and provides excellent protection against diseases caused by those four types. The 9-valent HPV vaccine includes all of the same HPV types while adding protection against five additional high-risk types, offering significantly broader coverage against HPV-related cancers.
The choice of vaccine should be based on several factors, including the individual’s age, previous HPV vaccination history, vaccine availability at the healthcare facility, and the recommendations of the treating physician.
Who Should Receive the HPV Vaccine?
Girls and Boys Before Exposure to HPV
The HPV vaccine provides the greatest benefit when administered before exposure to HPV. For this reason, the ACIP recommends vaccination beginning at age 9 years, with routine vaccination at 11–12 years of age for both girls and boys. Vaccination at this age allows the immune system to develop protection before the onset of sexual activity, which commonly occurs later in adolescence.
The Department of Disease Control, Ministry of Public Health of Thailand, includes HPV vaccination in the Expanded Program on Immunization (EPI) for Grade 5 schoolgirls nationwide. Individuals outside the national program who wish to receive the vaccine are encouraged to consult their healthcare provider and receive vaccination through hospitals or vaccination clinics.
Adolescents and Adults Who Have Not Completed Vaccination
Individuals who have never received the HPV vaccine or who have not completed the recommended vaccination series should consult a healthcare provider to determine the most appropriate schedule based on their age and medical history.
The ACIP recommends HPV vaccination for everyone through age 26 years if they have not been adequately vaccinated. For adults 27–45 years of age, vaccination is based on shared clinical decision-making, taking into account the individual’s potential risks and expected benefits.
Men Can Also Benefit From HPV Vaccination
HPV vaccination is not only for women. HPV is also responsible for several diseases in men, including genital warts, anal cancer, and certain cancers of the head and neck. Vaccinating men helps reduce their own risk of HPV-related diseases while also lowering the likelihood of transmitting HPV to their sexual partners.
The World Health Organization (WHO) recommends that countries consider expanding HPV vaccination programs to include both boys and girls, helping to strengthen herd immunity and improve population-wide protection against HPV infection.
Individuals at Increased Risk of HPV Infection or HPV-Related Disease
Certain groups should discuss HPV vaccination with their healthcare provider, including individuals with multiple sexual partners, those who have already become sexually active but have never been vaccinated, people with a history of sexually transmitted infections, individuals with weakened immune systems, and those seeking protection against HPV types they have not yet encountered.
When assessing eligibility, physicians may consider previous Pap smear results, HPV DNA test findings, vaccination history, and other relevant risk factors before making an individualized recommendation.
How Many Doses of the HPV Vaccine Are Needed?
Vaccination Started Before Age 15: Usually a 2-Dose Schedule
Individuals who begin HPV vaccination before the age of 15 years are generally recommended to receive two doses. The second dose should be administered at least six months after the first dose, and preferably within 6–12 months. Studies have shown that the immune response in this age group is sufficiently strong for a two-dose schedule to provide protection comparable to the three-dose schedule used in older individuals.
If the second dose is given less than five months after the first dose, a third dose may be required, depending on the physician’s assessment and current vaccination recommendations.
Vaccination Started at Age 15 or Older: Usually a 3-Dose Schedule
Individuals who begin HPV vaccination at 15 years of age or older are generally recommended to receive three doses, according to the following schedule.
Three-Dose HPV Vaccination Schedule
| Dose | Timing | Remarks |
|---|---|---|
| Dose 1 | Day 0 | Start of the vaccination series |
| Dose 2 | Month 2 (1-2 months after Dose 1) | At least 4 weeks after Dose 1 |
| Dose 3 | Month 6 (6 months after Dose 1) | At least 12 weeks after Dose 2 |
This schedule allows the immune system to develop optimal and long-lasting protection. If a scheduled dose is delayed, the vaccination series does not need to be restarted. Instead, the remaining dose(s) should be administered as soon as appropriate after consultation with a healthcare provider.
People with Weakened Immune Systems May Require Three Doses
Individuals with compromised immune function, including those living with HIV infection, receiving immunosuppressive therapy, or who have undergone organ transplantation, are generally advised to receive the three-dose schedule, even if vaccination is started before the age of 15. Because immune responses may be reduced in these individuals, two doses may not provide sufficient protection. The vaccination schedule should always be individualized based on the person’s medical condition and physician’s recommendation.
Consult a Doctor Before Vaccination
Before receiving the HPV vaccine, individuals should consult their healthcare provider to assess their age, overall health, previous vaccination history, personal risk factors, and the most appropriate vaccine type, whether the 4-valent HPV vaccine or the 9-valent HPV vaccine. A thorough discussion with a physician helps ensure informed decision-making and allows vaccination to be tailored to each individual’s circumstances.
Inform Your Doctor About Your Medical History and Allergies
Before vaccination, individuals should inform their physician or healthcare provider about the following:
- A history of allergy to vaccines or vaccine components, including yeast or other ingredients contained in HPV vaccines.
- Current pregnancy or plans to become pregnant, as HPV vaccination is not routinely recommended during pregnancy under current guidelines.
- Breastfeeding status.
- Underlying medical conditions and medications, particularly immunosuppressive drugs.
Inform Your Doctor About Previous HPV Vaccination
If you have previously received an HPV vaccine, inform your healthcare provider which vaccine you received, such as the 4-valent or 9-valent vaccine, how many doses you have completed, and when your most recent dose was administered. This information helps determine the most appropriate schedule for any remaining doses.
Individuals who have already completed the 4-valent HPV vaccine series should consult their physician to determine whether receiving the 9-valent vaccine would provide additional benefit based on their age, current risk factors, and individual circumstances.
Please inform us if you have a history of HPV infection or abnormal test results.
If you have previously been diagnosed with HPV infection, had an abnormal Pap smear or HPV DNA test, been diagnosed with abnormal cervical cells, or received treatment for genital warts, you should inform your physician before vaccination. HPV vaccination protects against HPV types that have not yet been acquired but does not treat existing infection or established lesions. This information allows your physician to accurately assess the potential benefits of vaccination.
Continue Recommended Cervical Cancer Screening
Women who are eligible for cervical cancer screening should continue to undergo screening according to their physician’s recommendations, including Pap smear or HPV DNA testing when appropriate. HPV vaccination does not replace routine cervical cancer screening, and the vaccine does not protect against every HPV type. Regular screening therefore remains essential, even after completing the recommended vaccination series.
Delay Vaccination If You Have a High Fever or Acute Illness
Individuals with a high fever, acute illness, significant fatigue, or severe infection should postpone vaccination until they have recovered. A healthcare provider should reassess their condition before scheduling vaccination. Minor illnesses, such as a common cold without fever, are generally not considered contraindications to HPV vaccination.
Get Adequate Rest and Eat Normally Before Vaccination
Before vaccination, individuals should get enough rest, eat their usual meals, and stay well hydrated. Fasting before vaccination is not recommended because it may increase the likelihood of dizziness, lightheadedness, or fatigue after the injection. After vaccination, individuals are advised to remain at the healthcare facility for 15–30 minutes so medical staff can monitor for any immediate reactions before they leave.
Bring Your Vaccination Record or Previous Medical Documents
If available, bring your vaccination record, vaccination certificate, Pap smear results, HPV DNA test reports, or other relevant medical records. These documents help healthcare providers plan appropriate vaccination, follow-up care, and future screening recommendations.
Side Effects of the 4-Valent and 9-Valent HPV Vaccines
Common Side Effects
The side effects of the 4-valent and 9-valent HPV vaccines are generally similar and are usually mild. Common reactions include:
- Pain, swelling, redness, or irritation at the injection site
- Mild fever, headache, or fatigue
- Nausea, dizziness, or lightheadedness, particularly immediately after vaccination
- Muscle aches or joint pain
According to the Centers for Disease Control and Prevention (CDC), these symptoms usually resolve on their own within a few days and generally do not require any specific treatment.
Does the 9-Valent HPV Vaccine Cause More Side Effects?
Overall, the side effect profile of the 9-valent HPV vaccine is not significantly different from that of the 4-valent vaccine. However, some clinical studies have reported that local injection-site reactions, such as pain, swelling, or redness, may occur slightly more frequently with the 9-valent vaccine. These reactions are generally mild, self-limiting, and resolve without treatment.
Long-term safety data from the Vaccine Adverse Event Reporting System (VAERS) and extensive post-marketing surveillance continue to demonstrate that HPV vaccines have an excellent safety profile.
Symptoms That Require Immediate Medical Attention
Individuals should seek immediate medical care if any of the following symptoms occur after HPV vaccination:
- Signs of anaphylaxis, including difficulty breathing, hoarseness, swelling of the face, lips, mouth, or throat
- Widespread hives or severe allergic rash
- Severe dizziness, fainting, or loss of consciousness while standing or walking
- A fever higher than 39°C (102.2°F)
- Pain, swelling, or redness at the injection site that does not improve within 3–5 days
Frequently Asked Questions: 4-Valent and 9-Valent HPV Vaccines
Q: Can I still receive the HPV vaccine if I have already had sex?
Direct answer: Yes. You can still consult a doctor about HPV vaccination because sexually active individuals may not have been exposed to every HPV type covered by the vaccine. The vaccine may still provide protection against HPV types that have not yet been acquired. However, vaccination offers the greatest benefit when given before any potential exposure to HPV.
Q: Should I receive the HPV vaccine if I have previously had an HPV infection?
Direct answer: A previous HPV infection does not mean that you have been exposed to every HPV type included in the vaccine. Vaccination may still help protect against other types you have not yet acquired. However, it cannot eliminate an existing infection or treat lesions that have already developed. An individual assessment by a doctor is therefore recommended.
Q: Do men need to receive the HPV vaccine?
Direct answer: Men can receive and benefit from HPV vaccination. The vaccine helps reduce the risk of genital warts, anal cancer, and certain HPV-related cancers of the head and neck. It may also reduce the likelihood of transmitting HPV to a sexual partner.
Q: Is the 9-valent HPV vaccine better than the 4-valent vaccine?
คำตอบตรง: วัคซีน HPV 9 สายพันธุ์ครอบคลุมสายพันธุ์มากกว่า โดยเพิ่ม HPV 31, 33, 45, 52 และ 58 ซึ่งเป็นกลุ่มเสี่ยงสูงเพิ่มเติม ทำให้ป้องกันมะเร็งปากมดลูกและมะเร็งที่เกี่ยวข้องได้ครอบคลุมกว่า อย่างไรก็ตาม การเลือกชนิดวัคซีนควรพิจารณาจากอายุ ประวัติวัคซีนเดิม และคำแนะนำของแพทย์ประกอบ
Q: Do I still need a Pap smear or HPV DNA test after receiving the HPV vaccine?
Direct answer: Yes. Cervical cancer screening should still be performed according to age and medical recommendations. Although HPV vaccination significantly reduces the risk of HPV-related disease, it does not protect against every HPV type and cannot provide 100% protection. Regular screening therefore remains essential.
Q: If I do not complete the HPV vaccine series, do I need to start again?
Direct answer: No. Individuals who have not completed the full vaccination series generally do not need to restart from the first dose. They should consult a doctor to arrange the remaining dose or doses according to an appropriate schedule, as the immune response developed from previous doses is not lost.
Q: Why should the HPV vaccine be given before the first sexual experience?
Direct answer: The HPV vaccine is designed to prevent infection rather than treat an existing infection. Vaccination before possible exposure allows the body to develop protective immunity before encountering the virus, providing the highest level of protection. Sexually active individuals may still benefit, but the overall benefit may be lower than in those vaccinated before exposure.
Frequently Asked Questions: 4-Valent and 9-Valent HPV Vaccines
| Topic | Details |
|---|---|
| Available vaccines | 4-valent HPV vaccine (Gardasil) and 9-valent HPV vaccine (Gardasil 9) |
| Main target groups | Girls and boys aged 9-26 years; vaccination may also be considered through age 45 |
| Number of doses | 2 doses when started before age 15 / 3 doses when started at age 15 or older |
| Three-dose schedule | Months 0, 2, and 6 |
| Diseases prevented | Cervical cancer, anal cancer, genital warts, and other HPV-related cancers |
| Main precautions or contraindications | Severe allergy to vaccine components, pregnancy, or high fever on the vaccination day |
| Observation period | Remain at the healthcare facility for 15-30 minutes after vaccination |
| Additional recommendation | Continue Pap smear and HPV DNA testing according to age, even after vaccination |
Vaccination Before Exposure Provides the Greatest Benefit
HPV vaccination is a proactive preventive measure that should ideally be considered before any potential exposure to the virus, particularly among adolescents and individuals who have not previously been vaccinated. Early vaccination can effectively reduce the future risk of HPV-related diseases.
The World Health Organization (WHO) has stated that if countries achieve HPV vaccination coverage of 90% among girls by 2030, eliminating cervical cancer as a rare disease could become an achievable goal for the next generation.
Consult a Doctor to Select the Most Appropriate HPV Vaccine
Before vaccination, a doctor should evaluate the individual’s age, general health, previous vaccination history, personal risk factors, and prevention goals. This assessment helps determine whether the 4-valent or 9-valent HPV vaccine is the most appropriate option for each person.
PSK Clinic provides HPV vaccination and cervical cancer screening services by doctors experienced in sexual health. Personalized consultations are available to help each patient develop an appropriate HPV prevention plan at PSK Clinic, Lat Phrao, Bangkok.
LINE: @pskclinic, Tel: 095-049-4142
