Cervical Cancer Series 02 How Does HPV Cause Cervical Cancer?
“I’ve heard that HPV is common and that most infections go away naturally. So how can it cause cervical cancer?”
Many people immediately worry about cervical cancer when they receive a positive HPV test result. This is understandable because HPV is known to be the primary cause of cervical cancer.
However, HPV infection does not lead directly to cancer.
Most HPV infections are controlled by the immune system and clear naturally or become undetectable. The concern arises when certain high-risk types of HPV remain in the cervix for a long time.
Persistent high-risk HPV infection can interfere with the mechanisms that regulate cell growth and division. If these effects continue and cellular damage accumulates over many years, high-grade precancerous lesions may develop. Some of these lesions can eventually progress to cervical cancer.
Understanding this process requires looking at more than whether HPV is present. The HPV type, whether the infection persists, and whether abnormal changes have developed in cervical cells must all be considered.
A Positive HPV Test Does Not Mean Cervical Cancer
HPV stands for human papillomavirus, a group of viruses that infect the skin and mucous membranes.
HPV infection is extremely common. Most sexually active people will be infected at some point in their lives, often without experiencing any noticeable symptoms.
However, detecting HPV does not mean that serious changes have already developed in cervical cells.
Most HPV infections are controlled by the immune system and generally clear or become undetectable within one to two years. Many people never realize they were infected.
The same is true when a high-risk HPV test comes back positive.
A positive result means that high-risk HPV has been detected. It does not mean that cervical cancer has been found.
To assess the actual risk, healthcare professionals consider whether the same high-risk HPV type continues to be detected and whether abnormal changes are present in cervical cells.
HPV infection can be the starting point in the development of cervical cancer, but cervical cancer is not the outcome of every HPV infection.
What Is the Difference Between Low-Risk and High-Risk HPV?
More than 200 types of HPV have been identified. Among those that infect the genital area, HPV types can be classified as low-risk or high-risk according to their association with cancer.
HPV types 6 and 11 are common examples of low-risk HPV. They mainly cause genital warts and are generally not associated with cervical cancer.
High-risk HPV types include 16 and 18, as well as types 31, 33, 45, 52, and 58. When infections with these types persist, the likelihood of abnormal changes developing in cervical cells may increase.
HPV types 16 and 18 are associated with approximately 70% of cervical cancers worldwide.
However, it is important to understand what “high-risk” means.
It does not mean that these HPV types cause cancer as soon as infection occurs. It means that they can cause cancer-related cellular changes when the infection persists over time.
A positive high-risk HPV result therefore does not mean that cervical cancer will inevitably develop.
In addition to the HPV type, one of the most important factors is how long the infection persists.
Why Does Persistent Infection Matter?
When HPV infects the cervix, it enters cells on the cervical surface.
In most cases, the immune system controls the infection, allowing the virus to clear or become undetectable. These temporary infections usually do not cause serious cellular changes.
Persistent high-risk HPV infections require closer attention.
When a high-risk HPV infection continues, proteins produced by the virus can repeatedly interfere with the normal mechanisms that regulate the growth and division of cervical cells. Over time, abnormal cells may be less likely to stop growing or be removed, allowing them to accumulate.
Factors such as smoking and a weakened immune system can increase the likelihood that HPV will persist or that abnormal cell changes will progress.
Persistent infection, however, does not mean that cervical cancer has already developed. It is a sign that the cervix should be monitored carefully for cellular changes.
The actual risk depends on several factors, including the HPV type, the duration of infection, and whether abnormal cervical cells are present.
The factor most closely associated with cervical cancer risk is not a single HPV infection, but a high-risk HPV infection that persists over time.
How Do E6 and E7 Interfere With the Cell’s Safety Systems?
Normal cells have built-in safety systems that prevent damaged cells from continuing to divide.
When a cell’s DNA is damaged, these systems can pause cell division and allow time for repair. If the damage is too severe to repair, they can trigger programmed cell death.
Two important proteins involved in these processes are p53 and RB.
The p53 protein acts like a safety inspector. It checks for DNA damage and, when a problem is detected, can stop cell division, support DNA repair, or help eliminate a severely damaged cell.
The RB protein acts like a brake that prevents cells from dividing when division is not needed.
High-risk HPV produces proteins called E6 and E7 that can interfere with these safety systems.
E6 promotes the breakdown of p53, weakening the cell’s ability to stop or eliminate damaged cells. As a result, damaged cells may survive when they normally would not.
E7 disrupts the function of RB. When this brake becomes less effective, abnormal cells can continue moving through the cell cycle and dividing.
Put simply, E6 weakens the system that identifies and removes damaged cells, while E7 interferes with the brake that prevents unnecessary cell division.
However, a normal cell does not become cancerous the moment E6 and E7 begin to act.
High-risk HPV must usually persist, cellular safeguards must remain disrupted, and additional genetic and cellular damage must accumulate before precancerous lesions or cervical cancer can develop.
How Do Normal Cervical Cells Change Over Time?
The progression from high-risk HPV infection to cervical cancer is not a single, straight path that everyone follows.
In most people, the immune system controls the infection and HPV clears or becomes undetectable.
In some people, however, the infection persists and abnormal changes develop in cervical cells. These may appear as low-grade changes or high-grade precancerous lesions.
Low-grade changes often resolve naturally. High-grade lesions can be detected through screening and treated before they progress to invasive cervical cancer.
If a high-risk HPV infection and high-grade cell changes persist without appropriate monitoring or treatment, some abnormal cells may eventually invade the tissue beneath the surface of the cervix. At this point, the condition has progressed to invasive cervical cancer.
The possible pathways can be understood as follows:
High-risk HPV infection
→ In most people: The infection clears or becomes undetectable
→ In some people: The infection persists
→ Low-grade changes or high-grade precancerous lesions may develop
→ Some untreated high-grade lesions persist or progress
→ Invasive cervical cancer may eventually develop
Cervical cell changes do not necessarily progress in sequence from CIN 1 to CIN 2 and then CIN 3.
At different stages, the infection or cellular changes may resolve. Screening also creates opportunities to detect, monitor, or treat abnormal changes before cancer develops.
There are several possible paths between HPV infection and cervical cancer, and most infections and cervical cell changes do not progress to cancer.
How Is CIN Different From Cervical Cancer?
CIN is a term used to describe abnormal changes in cervical cells.
CIN stands for cervical intraepithelial neoplasia.
CIN refers to abnormal changes confined to cells on the surface of the cervix. Unlike invasive cervical cancer, these cells have not invaded deeper tissue.
CIN 1 is considered a low-grade change and often resolves naturally. CIN 2 and CIN 3 are generally classified as high-grade precancerous lesions because they have a greater potential to progress to cancer.
However, CIN 2 and CIN 3 are still not the same as invasive cervical cancer. When these lesions are detected and appropriately monitored or treated, progression to cervical cancer can often be prevented.
Not all CIN progresses to cervical cancer, and not every lesion advances in order from CIN 1 to CIN 2 and then CIN 3.
CIN is not cancer itself. It is a cellular change that may require monitoring or treatment because of its potential to progress.
The meaning of each CIN grade and how these changes are managed will be discussed in detail in Cervical Cancer Series 05, “What Is CIN?”
Why Does Cervical Cancer Usually Take Years to Develop?
Persistent high-risk HPV infection does not cause cervical cancer immediately.
The mechanisms that regulate cell growth and division must remain disrupted over time. Abnormal cells must survive and continue multiplying while additional genetic and cellular damage gradually accumulates.
This is why cervical cancer does not typically develop soon after HPV infection.
According to the World Health Organization, it usually takes 15 to 20 years for abnormal cervical cells to develop into cancer in people with normal immune function. In people with severely weakened immune systems, the process may take approximately 5 to 10 years.
These time frames do not apply equally to everyone.
The likelihood and speed of progression can vary according to the HPV type, how long the infection persists, immune status, smoking, and whether appropriate screening and treatment are received.
A recent positive HPV test therefore does not mean that cervical cancer will develop soon. At the same time, the absence of symptoms does not mean that persistent infection or abnormal cellular changes can safely be ignored.
HPV does not instantly transform a normal cervical cell into a cancer cell. Cervical cancer develops in only some people, usually after high-risk HPV persists and cellular damage accumulates over many years.
The time this process takes creates an important opportunity to prevent cervical cancer.
This Long Process Creates an Opportunity for Screening
The long time it usually takes for cervical cancer to develop creates an important opportunity for prevention.
Cervical cancer screening is not designed solely to find cancer that has already developed.
Screening can identify high-risk HPV and abnormal changes in cervical cells. When high-grade lesions are found before they become cancer, appropriate monitoring and treatment can prevent progression to invasive cervical cancer.
An abnormal HPV or Pap test result should therefore not automatically be interpreted as a cancer diagnosis or become a reason for overwhelming fear.
At the same time, recommended follow-up testing should not be delayed simply because there are no symptoms.
Because progression from HPV infection to cervical cancer usually takes years, regular screening provides opportunities to find precancerous changes while they can still be monitored or treated.
The different screening tests, when screening should begin, and how often it is recommended will be explained in the next article, “When Should Cervical Cancer Screening Begin?”
Key Takeaways
A positive HPV test does not mean that cervical cancer has been found.
Most HPV infections are controlled by the immune system and clear or become undetectable within one to two years.
The main concern is a high-risk HPV infection that persists over time.
The E6 and E7 proteins produced by high-risk HPV can interfere with cellular safeguards involving p53 and RB. If this disruption continues and further damage accumulates, precancerous lesions may develop and, in some cases, progress to cervical cancer.
CIN refers to abnormal cells confined to the surface of the cervix. CIN 1 is a low-grade change, while CIN 2 and CIN 3 are generally considered high-grade precancerous lesions. CIN is not the same as invasive cervical cancer.
Most HPV infections and cervical cell changes do not progress to cancer. These changes also do not necessarily advance in order from CIN 1 to CIN 2 and then CIN 3.
Because cervical cancer usually develops over many years, regular screening can detect abnormal changes before they become cancer.
If you receive an abnormal HPV or Pap test result, do not assume that it means cancer. Follow your healthcare professional’s guidance and complete any recommended follow-up tests.
In the next article, “When Should Cervical Cancer Screening Begin?” we will examine the differences between Pap and HPV tests, when screening should start, and how often it is recommended.
References
World Health Organization. “Cervical Cancer.”
https://www.who.int/news-room/fact-sheets/detail/cervical-cancerWorld Health Organization. “Human Papillomavirus and Cancer.”
https://www.who.int/news-room/fact-sheets/detail/human-papilloma-virus-and-cancerNational Cancer Institute. “Cervical Cancer Causes, Risk Factors, and Prevention.”
https://www.cancer.gov/types/cervical/causes-risk-preventionCenters for Disease Control and Prevention. “About Genital HPV Infection.”
https://www.cdc.gov/sti/about/about-genital-hpv-infection.htmlCenters for Disease Control and Prevention. “Chapter 11: Human Papillomavirus.” Epidemiology and Prevention of Vaccine-Preventable Diseases.
https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-11-human-papillomavirus.htmlNational Cancer Institute. “Definition of Cervical Intraepithelial Neoplasia.” NCI Dictionary of Cancer Terms.
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/cervical-intraepithelial-neoplasiaNational Cancer Institute. “Understanding Cervical Changes: A Health Guide.”
https://www.cancer.gov/types/cervical/screening/abnormal-hpv-pap-test-results/understanding-cervical-changes.pdfInternational Agency for Research on Cancer. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Human Papillomaviruses.
https://publications.iarc.who.int/Book-And-Report-Series/Iarc-Monographs-On-The-Identification-Of-Carcinogenic-Hazards-To-Humans/Human-Papillomaviruses-2007
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