It is possible to have cervical cancer even with a negative Human Papillomavirus (HPV) test result, although this scenario is uncommon. Cervical cancer is a malignancy that forms in the tissues of the cervix, the lower part of the uterus connecting to the vagina. While screening programs have significantly lowered the incidence of this disease, a negative HPV test does not entirely eliminate the small possibility of cancer being present. Understanding HPV-negative cervical cancers highlights the limitations of current screening technology.
The Relationship Between HPV and Cervical Cancer
The vast majority of cervical cancer cases are directly linked to persistent infection with high-risk types of the human papillomavirus (HPV). The cancer-causing process begins when the virus, specifically high-risk types like HPV 16 and 18, establishes a long-term infection in the cells of the cervix. This persistent infection leads to changes in the cervical cells, gradually progressing to precancerous lesions over 10 to 20 years. HPV 16 and 18 alone are responsible for approximately 70% of cervical cancer cases worldwide, making them the primary targets of vaccination and screening efforts. Regular screening is designed to detect these precancerous changes before they become invasive cancer.
Screening Methods and Test Accuracy
Cervical cancer screening typically involves two primary tests: the Pap test and the HPV test. The Pap test examines collected cervical cells for abnormal changes, which may indicate precancerous or cancerous cells. The HPV test specifically looks for the DNA of the high-risk HPV types known to cause cancer. Many screening programs use co-testing, combining both tests to maximize detection accuracy. A negative result on both tests gives a high level of reassurance, allowing for a longer interval between screenings, typically five years for women over 30. Although the HPV test is highly sensitive, no screening method is perfectly accurate, and the small chance of an undetected cancer remains.
Mechanisms Behind a Negative HPV Result
A negative HPV test result in the presence of cervical cancer is rare, usually explained by the tumor’s biology or limitations in the testing process. Squamous cell carcinoma, which accounts for about 70% of cases, is almost always HPV-positive.
Tumor Biology
The second most common type, adenocarcinoma, forms in the glandular cells deeper in the cervical canal. This type is less frequently associated with the high-risk HPV types detected by commercial assays; up to 38% of cervical adenocarcinomas may test negative for HPV. Furthermore, some rare, non-squamous cell subtypes, such as clear cell or gastric-type adenocarcinomas, are strongly associated with being genuinely HPV-negative.
Technical Limitations
Technical issues can also contribute to a false-negative result, even if the virus is present. Sampling error occurs when the collection procedure does not adequately capture cells from the affected area. The viral load may also be too low or localized to be detected by the assay. Another element is that the specific high-risk HPV strain causing the cancer may not be included in the panel of types tested by the commercial assay.
Diagnostic Follow-Up and Symptom Evaluation
Regardless of any negative screening test result, any unexplained or persistent symptoms should prompt an evaluation by a healthcare provider. Symptoms that warrant investigation, even if a recent screening was negative, include:
- Bleeding after intercourse.
- Bleeding between periods.
- Post-menopausal bleeding.
- Pelvic pain or pain during intercourse.
If cancer is suspected, the doctor will likely recommend a colposcopy. This procedure uses a specialized magnifying instrument to closely examine the cervix. A small tissue sample, known as a biopsy, is taken for laboratory examination. Tissue confirmation through a biopsy is the only way to definitively diagnose cervical cancer, as screening tests are designed to find risk and pre-cancers.