Cervical cancer originates in the cells of the cervix, the lower part of the uterus that connects to the vagina. It typically develops slowly, often preceded by abnormal cell changes that can progress into cancer if left untreated. While strongly associated with human papillomavirus (HPV), a common sexually transmitted infection, the question arises whether cervical cancer can develop without its presence.
The Overwhelming Link to HPV
Human Papillomavirus (HPV) is the primary cause of most cervical cancers, accounting for 95% of cases worldwide. HPV includes over 100 types, with about 40 transmitted sexually. High-risk HPV types, particularly HPV 16 and HPV 18, cause 70% to 80% of these cancers.
Persistent infection with these high-risk HPV types drives the cellular changes in the cervix that can lead to cancer. HPV proteins, specifically E6 and E7, interfere with tumor suppressor genes like p53 and Rb, which normally regulate cell growth and death. This disruption allows cervical cells to multiply uncontrollably, leading to abnormal cells known as dysplasia or precancers. If these precancerous cells are not detected and treated, they can progress to invasive cervical cancer over a period that can range from 5 to 20 years.
Cervical Cancer Beyond HPV
While the vast majority of cervical cancers are linked to HPV, it is possible, though rare, to develop cervical cancer without detectable HPV. These cases, known as HPV-negative cervical cancers, account for 3% to 11% of diagnoses. Their precise causes are under investigation, but may involve genetic mutations or other factors.
HPV-negative cervical cancers are more frequently adenocarcinomas, originating in the glandular cells of the cervix, rather than the more common squamous cell carcinomas. Rare subtypes like gastric-type, clear cell, or mesonephric adenocarcinomas are also more likely to be HPV-negative. These less common cancers can be harder to detect early, often developing in areas of the cervix more difficult to access during routine screenings. An HPV infection might have been present in the past but cleared by the immune system, leaving behind cellular damage that later progressed to cancer, even without current viral detection.
Other Contributing Risk Factors
Several other factors can increase a person’s risk of developing cervical cancer, either independently or in combination with HPV infection. Smoking is a significant risk factor, as tobacco chemicals can damage cervical cell DNA and weaken the immune system’s ability to clear HPV infections. Women who smoke are two to five times more likely to develop cervical abnormalities and cervical cancer compared to non-smokers.
A weakened immune system, whether due to conditions like HIV infection or immunosuppressive medications after organ transplantation, also increases susceptibility. A compromised immune response makes it more difficult for the body to fight off HPV, allowing persistent infections to develop and accelerate the progression of precancerous cells to cancer. Long-term use of oral contraceptives has been associated with a slightly increased risk, possibly by making cervical cells more vulnerable to HPV. This risk declines after discontinuing use. Having multiple full-term pregnancies has been linked to a higher risk, potentially due to hormonal changes or physical trauma to the cervix, though this association is primarily observed with HPV infection. A family history of cervical cancer can also indicate a slightly increased risk, possibly due to inherited genetic predispositions that affect the immune response to HPV.
Prevention and Early Detection
Since cervical cancer can occur without HPV and other risk factors exist, a comprehensive approach to prevention and early detection is important. Regular cervical cancer screenings, including Pap tests and HPV tests, effectively identify precancerous changes before they become cancerous, regardless of the underlying cause. Pap tests examine cervical cells for abnormalities, while HPV tests specifically look for high-risk HPV types. Current guidelines recommend primary HPV testing every five years for individuals aged 25 to 65, or co-testing (HPV and Pap test) every five years.
HPV vaccination is a primary preventive measure for the most common types of cervical cancer. Vaccines target high-risk HPV types, particularly HPV 16 and 18. While vaccination does not protect against all HPV types or the rare HPV-negative cancers, it significantly reduces the overall risk of developing the disease. Adopting healthy lifestyle choices, such as avoiding smoking, maintaining a balanced diet, and regular physical activity, can also contribute to a stronger immune system and reduce overall cancer risk.