How HPV Can Lead to Cancers

Introduction

Human Papillomavirus (HPV) is the most common sexually transmitted infection (STI) worldwide, with nearly 80% of the global population exposed by the age of 50¹. While the immune system clears most HPV infections (within 1 to 2 years), persistent infection can be hazardous to health^2,3.  

There are over 200 known subtypes of HPV that are broadly categorised into low-risk and high-risk types, with around 40 subtypes affecting the genital tract^2,4. Low-risk types, such as HPV 6 and 11, typically cause benign (non-cancerous) conditions like genital warts. In contrast, persistent infection with high-risk types (most notably HPV 16 and 18) can lead to precancerous lesions and malignancies. High-risk HPV types are associated with various cancers, including cervical, anal, oropharyngeal (back of the throat), and penile cancers³. 

Vaccines are available and effective in preventing infection with the most common low and high-risk HPV types. However, global vaccination coverage still remains suboptimal^1,3. Therefore, understanding the link between persistent HPV infection and cancer is critical for prevention, early detection, and treatment strategies. 

How Is HPV Transmitted

HPV is mainly spread through skin-to-skin contact, especially during sexual activity. Here’s how transmission can happen: 

• Sexual contact: HPV is most often passed through mucocutaneous contact during sexual activity (vaginal, anal, or oral) with an HPV infected person. It is important to note that even without visible symptoms, the virus can still spread⁵.  
• Genital skin contact: HPV can be transmitted through close genital contact, even without penetration. Using shared sex toys (insertive types) can also carry risks⁵. 
• Oral and anal sex: The virus can spread to the mouth and throat or the anus, especially with unprotected oral or anal sex⁵.
• Self-inoculation: A person may transfer the virus from one part of their body to another, such as from the genitals to the mouth, by touch⁵.
• Mother-to-child transmission (rare): An infected mother may pass HPV to her baby during childbirth, which can sometimes lead to throat warts in the baby⁵. 

Symptoms of HPV

Most people infected with HPV may not experience any symptoms. They may not even be aware that they have the virus. When symptoms do appear, they depend on the type of HPV involved. Common signs and symptoms include: 

• Low-risk HPV types: These may lead to genital warts (small, rough, skin-coloured growths) that can appear on the vagina, penis, or anus and also cause symptoms such as itching, discomfort, or bleeding in the affected area. Rarely, they may also cause lumps on the throat (known as respiratory papillomatosis)^2,3. 
• High-risk HPV types: These strains can cause cellular changes that may slowly and gradually develop into cancer (over many years). These changes (early lesions) may not produce noticeable symptoms in the beginning. However, if the infection persists and progresses to advanced-stage HPV, it can eventually cause symptoms such as pain, bleeding, or noticeable lumps, depending on the location of the cancer (e.g., cervix, anus, or throat)⁶. 

How Does HPV Cause Cancer

HPV can cause cancer when high-risk types of the virus stay in the body for a long time and interfere with how normal cells grow and divide.  

In the early stages of an HPV infection, the virus multiplies in the skin or mucosal cells without immediately causing harm. Over time, when high-risk HPV types insert their genetic material into the human DNA, it leads to the constant production of oncoproteins. These are proteins produced by the virus that promote cancer growth by interfering with the growth and division of normal cells, which can eventually lead to abnormal or precancerous changes, and, if not treated, possibly cancer. 

These proteins produced by the virus disrupt the functioning of tumour-suppressor proteins, which are proteins present in the body cells that help with DNA repair, control the cell cycle, and prevent uncontrolled cell growth. The oncoproteins produced by HPV in the body are³: 

• E6, which promotes the degradation of p53  
• E7, which promotes the degradation of pRb (retinoblastoma protein) 

The inactivation of tumour-suppressor proteins p53 and pRb leads to impaired DNA repair mechanisms and loss of cell cycle control, creating conditions that cause uncontrolled cell growth and eventually cancer development.  

Note: It’s important to note that wart-like lesions are usually caused by low-risk HPV types and do not typically progress to cancer. In contrast, high-risk HPV types can cause abnormal cell changes (like cervical intraepithelial neoplasia or CIN), which may become cancerous if not detected and treated early³.

Different Types of Cancer Caused by HPV

Did you know that HPV is estimated to cause around 690,000 cancers worldwide each year⁶? 

Let us take a look at the types of cancers that are linked to HPV: 

1. Cervical Cancer

HPV and cervical cancer are very closely linked. This is because almost all cervical cancer cases are caused by HPV⁶.

2. Anal Cancer

More than 90% of anal cancer cases are caused by HPV⁶.

3. Oropharyngeal Cancer

About 70% of oropharyngeal cancers, which occur in the middle part of the throat behind the mouth, are linked to HPV⁶.

Note: People often confuse oropharyngeal cancer with mouth and throat cancer, but they are not the same; each affects different areas within the head and neck region. 

4. Vaginal Cancer

Approximately 75% of vaginal cancer cases are linked to HPV⁶.

5. Vulvar Cancer 

HPV is responsible for around 69% of vulvar cancer cases. This cancer affects the outer part of the female genitalia⁶.

6. Penile Cancer 

Around 63% of penile cancer cases are attributed to HPV. This rare cancer usually develops on or under the foreskin of the penis⁶.

Diagnosis Methods

Different types of HPV-related cancers have different diagnostic approaches. While some have well-established screening tests, others are detected only after symptoms appear or through targeted exams in high-risk individuals. 

1. Cervical Cancer

• Pap test (Pap smear): Detects abnormal cervical cell changes. 
• HPV test: Identifies high-risk HPV strains. 
• Co-testing: Combines Pap and HPV tests for more accurate screening. 
• Colposcopy: Follow-up procedure if screening tests are abnormal³. 

Note: Women should begin regular cervical cancer screening at age 30, with tests typically recommended every 5 to 10 years, depending on the type of test used and individual risk factors². 

2. Anal Cancer 

• Anal Pap test: Used primarily for high-risk groups (e.g., people with HIV, men who have sex with men)³. 
• High-resolution anoscopy (HRA): Examines the anal canal more closely if abnormal cells are found⁷. 

3. Oropharyngeal (Throat) Cancer

• Physical examination: Checks for lumps or lesions in the throat and neck³. 
• Imaging (CT, MRI, or PET scans): Used to assess the extent of disease^7,8. 

4. Vaginal Cancer

• Pelvic exam: May detect abnormalities³. 
• Pap test or colposcopy: May occasionally identify vaginal cancer, though not designed for this purpose^8,9. 

5. Vulvar Cancer 

• Visual and physical exam: Inspection for any visible changes or lesions¹⁰. 

6. Penile Cancer 

• Visual and physical exam: Inspection of the penis for visible lesions or growths¹¹. 

Note: In all cases, a biopsy is done to confirm the diagnosis if any abnormalities are found. 

When to See a Doctor

While most HPV infections go away on their own without causing symptoms, some can lead to serious health issues if left untreated. Knowing when to seek medical advice is key to early detection and prevention. You should see a doctor if you experience: 

• Visible genital warts (often caused by low-risk HPV types) 
• Unusual bleeding, especially between periods or after sex (can be a sign of cervical changes associated with high-risk HPV infection)²Â 
• Persistent pelvic, anal, or throat pain (may likely to occur in advanced stages of HPV-related disease)³  

Unusual vaginal discharge or foul odour (Although these may not be specific to HPV and are commonly linked to other infections like bacterial vaginosis, still these warrant medical evaluation)²Â 

Note: It’s important to follow regular screening schedules based on your age and risk factors to detect any HPV-related changes early. 

Vaccines Available

HPV vaccination offers safe, effective, and long-lasting protection against the most cancer-causing HPV infections, especially when given before exposure. Three types of HPV vaccines have been developed, each protecting against different numbers of HPV types^12,13: 

• Bivalent (Cervarix): Protects against HPV types 16 and 18, the most common high-risk types linked to cervical cancer. 
• Quadrivalent (Gardasil): Covers types 6, 11, 16, and 18, protecting against both cancer-causing and wart-causing types. 
• 9-valent (Gardasil 9): The most comprehensive, covering HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, offering broader protection against cancers and genital warts. 

Also Read: Human Papillomavirus (HPV): What Is It, Causes, Symptoms, and Prevention

Conclusion

Despite being a common viral infection, the majority of HPV-related cancers are preventable through regular screenings and timely vaccination. Therefore, it is important to raise awareness about HPV, its risks, and the need for early detection and vaccination in reducing the incidence of these cancers.  Routine screening helps detect abnormal cell changes early, allowing for prompt treatment and improved outcomes. At the same time, HPV vaccination offers strong protection against high-risk strains, particularly when administered before exposure. These measures can help contribute to reducing the global burden of HPV as well as ensure better long-term health for individuals and communities alike. 

Frequently Asked Questions (FAQs)

 References

1. Hathaway JK. HPV: diagnosis, prevention, and treatment. Clin Obstet Gynecol. 2012 Sep;55(3):671-80. Available from: https://dx.doi.org/10.1097/GRF.0b013e31825caa36 
2. World Health Organization. Human papillomavirus and cancer [Internet]. World Health Organization; 2024 Mar 5 [cited 2025 Jun 10]. Available from: https://www.who.int/news-room/fact-sheets/detail/human‑papilloma‑virus‑and‑cancer 
3. Luria L, Cardoza-Favarato G. Human Papillomavirus [Internet]. StatPearls Publishing. 2025 Jan; [updated 2023 Jan 16; cited 2025 Jun 10]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448132/ 
4. Gong P, Shi B, Cong X, Yang L, Gong C, Zhou Y, Li X, Wang J. Multiple infections containing the top five prevalent HPV genotypes and their impact on cervical lesions in Changzhou, China. Hum Vaccin Immunother. 2023 Aug 1;19(2):2245723. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10435003/ 
5. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Human papillomaviruses. Lyon (FR): International Agency for Research on Cancer; 2007. (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 90.) 1, Human papillomavirus (HPV) infection [Internet]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK321770/ 
6. National Cancer Institute. HPV and Cancer [Internet]. Bethesda (MD): National Cancer Institute; [updated 2023 Oct 18; cited 2025 Jun 10]. Available from: https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-and-cancer 
7. Wells J, Flowers L, Mehta CC, Chandler R, Knott R, McDonnell Holstad M, Watkins Bruner D. Follow-Up to High-Resolution Anoscopy After Abnormal Anal Cytology in People Living with HIV. AIDS Patient Care STDS. 2022 Jul;36(7):263-271. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9464048/ 
8. Avery EW, Joshi K, Mehra S, Mahajan A. Role of PET/CT in Oropharyngeal Cancers. Cancers (Basel). 2023 May 8;15(9):2651. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10177278/ 
9. Cooper DB, Dunton CJ. Colposcopy [Internet]. StatPearls Publishing. 2025 Jan; [updated 2023 Nov 12; cited 2025 Jun 10]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK564514/ 
10. Capria A, Tahir N, Fatehi M. Vulvar cancer [Internet]. StatPearls Publishing. 2025 Jan; [updated 2023 Jan 9; cited 2025 Jun 10]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK567798/ 
11. Engelsgjerd JS, Leslie SW, LaGrange CA. Penile cancer and penile intraepithelial neoplasia [Internet]. StatPearls Publishing. 2025 Jan; [updated 2024 Sep 2; cited 2025 Jun 10]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499930/ 
12. Centers for Disease Control and Prevention. HPV Vaccination [Internet]. Centers for Disease Control and Prevention; [updated 2024 Aug 20; cited 2025 Jun 10]. Available from: https://www.cdc.gov/hpv/vaccines/index.html 
13. Bergman H, Buckley BS, Villanueva G, et al. Comparison of different human papillomavirus (HPV) vaccine types and dose schedules for prevention of HPV-related disease in females and males. Cochrane Database Syst Rev. 2019 Nov 22;2019(11):CD013479. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC6873216/ 

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