HPV16 and HPV18 — The Most Cancer-Causing HPV Strains

Human Papillomavirus, or HPV, is one of the most common viruses found in humans and can be transmitted through sexual contact—even between healthy partners. There are over a hundred known types, but only a few are capable of causing cancer. Among them, HPV16 and HPV18 are considered the most dangerous and are the focus of global medical attention.

These two strains are responsible for more than 70% of cervical cancer cases and are also linked to cancers of the mouth, throat, anus, and penis. What makes them concerning is that they often show no symptoms, allowing the infection to persist silently for years.

This article will help you understand why HPV16 and HPV18 are more dangerous than other strains, which cancers they are associated with, and how you can detect and prevent them effectively—so you can take control of your long-term health with confidence.

What Are HPV16 and HPV18, and Why Are They Considered “High-Risk Strains”?

Human Papillomavirus (HPV) is a common sexually transmitted virus that affects both men and women. There are more than 100 known HPV types, but only a few are classified as high-risk because they can cause cellular changes that may develop into cancer.

Among these, HPV16 and HPV18 are the two most dangerous strains, responsible for over 70% of cervical cancer cases worldwide. They are also linked to cancers of the mouth, throat, anus, and penis.

The concerning part is that infections with these strains usually show no symptoms, allowing the virus to persist silently for years while gradually causing cellular damage without any warning signs.

The Mechanism of HPV16 and 18 — Why They Cause More Severe Cancers

HPV types 16 and 18 are classified as high-risk strains because they have the ability to integrate their genetic material into human cells. Once the virus enters the body, special viral proteins called E6 and E7 interfere with key genes that control normal cell division.

The E6 protein inactivates the p53 gene, which normally stops damaged cells from dividing or triggers them to self-destruct. Meanwhile, the E7 protein disrupts the Rb (Retinoblastoma) protein, a vital regulator that keeps cell growth under control. When both genes are silenced, cells begin to divide abnormally and can eventually become cancerous.

This process takes years to develop. The virus gradually alters the structure of epithelial cells, explaining why HPV-related cancers often progress silently and remain undetected in their early stages.

Cancers Associated with HPV16 and HPV18 in Men and Women

HPV16 and HPV18 are responsible for the majority of HPV-related cancers, especially cervical cancer — accounting for more than 70% of global cases, according to the World Health Organization (WHO).

In women, HPV16 is most commonly linked to squamous cell carcinoma of the cervix, while HPV18 is frequently associated with adenocarcinoma, a type that is harder to detect through routine Pap smears. These strains are also connected to cancers of the vagina and vulva.

In men, HPV16 plays a major role in oropharyngeal and oral cancers, as well as anal and penile cancers, often due to persistent infections that remain undiagnosed for years.

These two strains account for the majority of HPV-related cancers in both men and women, making early screening and prevention essential for long-term protection.

Why HPV18 Is Harder to Detect — Even When Pap Smear Results Are Normal

HPV18 is often associated with adenocarcinoma of the cervix, a cancer that begins in glandular cells located deeper within the cervical canal. Unlike squamous cell carcinoma, which forms on the outer surface, these deeper cells are harder to sample during a routine Pap smear.

Adenocarcinoma also tends to develop more slowly and may not show obvious cellular changes in the early stages. As a result, Pap smear results can appear “normal” even when HPV18 infection is already present.

Current recommendations from the World Health Organization (WHO) and the Royal Thai College of Obstetricians and Gynaecologists advise using HPV DNA testing or Co-testing (Pap + HPV DNA) to improve detection accuracy—especially for women aged 30 and above, or those with prior normal Pap results but ongoing risk factors.

Should Men Be Concerned About HPV16 and the Risk of Throat Cancer?

Although HPV is often discussed in relation to women, men can also contract HPV16, and infection rates have been increasing globally — particularly among men aged 30–55 with multiple sexual partners or inconsistent condom use.

In men, HPV16 is strongly linked to oropharyngeal (throat) cancer, a type of cancer that has risen significantly over the past decade. Studies show that over 90% of HPV-positive throat cancers are caused by HPV16. The virus is also connected to anal and penile cancers.

What makes HPV16 concerning for men is that it often causes no visible symptoms or lesions, making early detection difficult. Infection can persist silently until symptoms such as chronic sore throat, difficulty swallowing, or neck lumps appear — potential early warning signs of cellular changes that may lead to cancer.

Can HPV16 or HPV18 Infections Go Away on Their Own?

In most cases, the human body can clear HPV infections naturally within 1–2 years, especially in individuals with a healthy immune system. Early-stage infections often cause no symptoms and may resolve without any medical treatment.

However, HPV16 and HPV18 are more likely to persist compared to other strains. A persistent infection can significantly increase the risk of developing high-grade precancerous lesions or cancer—particularly in women over 30, smokers, or those with weakened immunity.

While some infections do go away naturally, it’s impossible to predict who will clear the virus completely. Regular screening and follow-up remain the safest approach to detect and prevent HPV-related complications early.

How Effective Is the HPV Vaccine Against Types 16 and 18?

The HPV vaccine is specifically designed to protect against the most dangerous strains — HPV16 and HPV18 — which together cause over 70% of cervical cancer cases worldwide. In Thailand, commonly used vaccines such as Cervarix (2-valent) and Gardasil / Gardasil 9 (4-valent and 9-valent) directly target these two high-risk types.

According to data from the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), completing the full vaccination schedule can reduce HPV16 and 18 infections by more than 90%, and significantly lower the incidence of high-grade precancerous lesions (CIN2/3), which are early indicators of cervical cancer.

The vaccine also benefits men by reducing the risk of HPV16-related cancers, including those of the throat, anus, and penis. While effectiveness may vary depending on age and immune response, vaccination before the onset of sexual activity offers the highest level of protection.

Who Should Get Screened or Vaccinated — and Which Test Is Recommended in 2025

As of 2025, HPV prevention and screening guidelines have been updated to better suit different age groups and individual risk profiles. Medical experts recommend that all women aged 25 and above undergo regular HPV screening — even if they have no symptoms or previously normal Pap results.

The primary test now is the HPV DNA Test, which directly detects the virus’s genetic material and offers greater accuracy than traditional Pap smears. Some women, particularly those aged 30 and above or with prior abnormal results, may benefit from Co-testing (Pap + HPV DNA) for enhanced sensitivity.

For vaccination, it’s best to start between the ages of 9–26, when the immune response is strongest. Both males and females can receive the vaccine. Adults over 26 can still get vaccinated if they’ve never been infected, but should first consult a doctor to assess suitability and determine the appropriate dosing schedule.

Conclusion

HPV16 and HPV18 are responsible for most HPV-related cancers in both men and women. Although many infections clear naturally, these high-risk types can persist for years and silently cause cellular changes that may develop into cancer later on.

Regular screening and vaccination remain the most effective ways to protect yourself. The HPV vaccine helps prevent infection and significantly reduces cancer risk, while the HPV DNA test allows early detection of potential abnormalities before any symptoms appear.

If you’ve never been screened or are unsure about vaccination, consulting a medical specialist is the safest and most proactive step you can take today — because prevention now could mean protection for your future health.

FAQ — Common Questions About HPV16 and HPV18

Does a normal Pap smear mean I’m free from HPV18?

Not necessarily. HPV18 often causes adenocarcinoma, which develops deeper in the cervix. A standard Pap smear may not collect enough cells from that area, so an HPV DNA test is recommended for more accurate detection.

Can men with HPV16 develop cancer?

Yes. HPV16 is linked to cancers of the throat, mouth, and anus, and cases of HPV-related throat cancer in men are rising globally. Men experiencing chronic sore throat or difficulty swallowing should consider screening.

Can HPV16 or HPV18 clear on their own?

In many cases, the body clears the virus naturally within 1–2 years. However, persistent infections lasting over two years can increase the risk of precancerous changes or cancer, so medical follow-up is essential.

Do HPV vaccines protect against all types of the virus?

No. Current vaccines mainly protect against HPV16 and HPV18, the two most dangerous strains, while newer versions like Gardasil 9 also cover additional high-risk types.

How often should HPV screening be done?

Screening is generally recommended every 3–5 years, depending on age and previous results. Those over 30 or with a history of abnormal tests should screen more frequently under medical guidance.

Reference

1. WHO — ความสัมพันธ์ HPV กับมะเร็ง Human papillomavirus and cancer — ให้ข้อมูลว่า HPV เป็นตัวการสำคัญของหลายมะเร็ง และบทบาทของ HPV16/18
2. NCI / Cancer.gov — สัดส่วน HPV16 และ HPV18 ก่อมะเร็งปากมดลูก HPV and Cervical Cancer — ระบุว่า HPV16 & HPV18 ก่อมะเร็งปากมดลูก ~70%
3. CancerResearchUK — ข้อมูลสาย HPV ที่ก่อมะเร็ง Risks And Causes Of Cervical Cancer — HPV16 + HPV18 ก่อ ~70% ของมะเร็งปากมดลูก
4. Nature / PMC / บทความทางวิชาการเกี่ยวกับการตรวจ E6/E7 mRNA. HPV E6/E7 mRNA test for the detection of high grade cervical lesions — บทวิจารณ์ประสิทธิภาพการตรวจ mRNA E6/E7
5. WHO Guideline — แนวทางการคัดกรอง & การใช้ HPV mRNA / DNA test WHO guideline for screening and treatment of cervical pre-cancer — แนะแนวใช้ HPV mRNA หรือ DNA tests
6. PMC บทความ HPV18 และความชุกใน SCC / ADC Human papillomavirus 18 Genetic Variation and Cervical Cancer — ให้ข้อมูลว่า HPV18 เป็นสายพันธุ์ carcinogenic อันดับสอง และสัดส่วนใน adenocarcinoma
7. CDC — มะเร็งที่สัมพันธ์กับ HPV Cancers Associated with Human Papillomavirus — ระบุจำนวนมะเร็งที่สัมพันธ์กับ HPV รวมทั้งบทบาทของ 16/18

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