PathAdvantage Journal

The FDA approval of at-home HPV testing is being marketed as a paradigm shift in cervical cancer screening, touting benefits such as superior convenience, accessibility and comfort.  

However, while at-home HPV testing addresses barriers to traditional in-clinic visits, it cannot replace more tried, tested and comprehensive screening methods like the Pap test for detecting pre-cancers and cancers. When considering at-home HPV testing, it is very important to also consider the significant concerns raised by medical professionals regarding the use of HPV testing as the sole method of cervical cancer screening (also called primary HPV testing).

 

The Benefits of At-Home HPV Testing 

This drive towards at-home testing is largely fueled by the desire to improve screening rates, which is admirable. For many, a traditional Pap test in a clinic can be difficult to schedule due to transportation, childcare arrangements and time constraints. For others, the traditional Pap test may induce anxiety and stress. At-home HPV tests potentially offer privacy, comfort, convenience and accessibility (particularly for those who live in rural areas), which are all valid advantages that could potentially help more people be screened for HPV. 

 

The Risks of Primary HPV Testing

However, sole reliance on primary HPV testing over the Pap test could be dangerous. A deeper look at the science behind the test, as well as professional opinions, reveals substantial problems with the sole reliance of cancer screening on HPV testing. Many medical organizations and pathologists, including the College of American Pathologists (CAP), the American Society for Clinical Pathology (ASCP), advocates like Nancy Brinker (founder of the Susan G. Komen breast cancer foundation) and the Black Women’s Health Imperative, express strong resistance to using HPV testing alone as a primary screening method. Their concerns, and ours at PathAdvantage, are multifaceted and focus on the potential for missed cancers and the loss of valuable diagnostic information.

1.  Increased Risk of Missed Cancers:

A major contention is that primary HPV testing alone could miss a significant number of cervical cancers. Compared to co-testing (which combines an HPV test with a Pap test, and involves direct visual and microscopic examination of the cervical cells), studies indicate that: 

• Twice as many cervical cancers will be missed with primary HPV testing.
• One in five women with biopsy-proven cervical cancer had a previously negative HPV result (in a large study of over 250,000 patients). This means even with a negative HPV test, some cancers are still present.
• Twice as many women with adenocarcinoma (a type of cervical cancer that is increasing) could be missed with primary HPV screening.
• Nearly 10% of high-grade lesions or cancers were high-risk HPV negative, even when using a highly sensitive HPV test, according to PathAdvantage’s own data from 2020. 

2.  Limitations of DNA-Based HPV Tests:

At least one of the FDA approved ‘at home’ HPV tests involve DNA-based tests. While these DNA-based tests may detect the presence of HPV DNA, it also detects inactive, transient infections that the body will clear naturally. This makes them less specific for cervical cancer and precancerous lesions than newer mRNA-based tests (like the Aptima HPV test), which only detect HPV infections that are actively causing changes and are more likely to lead to cancer.

Furthermore, DNA-based tests can be unreliable if they target the L1 region of the HPV virus. In advanced cervical cancer, the L1 gene is often lost as the virus integrates into the host’s DNA, meaning the test might miss these severe cases. In fact, HPV DNA can be undetectable in about 10% of women with invasive cancer or precancerous lesions.

3.  The Irreplaceable Value of the Pap Test (Cytology):

The push for primary HPV screening often downplays the crucial role of the Pap test. While HPV testing identifies the virus, the Pap test examines the cells for abnormalities, which is vital for detecting pre-cancers and cancers directly. Omitting the Pap test means losing critical diagnostic information from a comprehensive “well-woman examination,” including:

• Detection of Infections: Pap tests often reveal other infectious organisms like Trichomonas vaginalis (which can be asymptomatic in up to 95% of cases), Herpes virus, Candida and signs of bacterial vaginosis.
• Hormonal Status: The appearance of squamous cells can provide insights into a woman’s hormonal status.
• Endometrial Cell Assessment: Observing endometrial cells can be important for detecting significant endometrial pathology, especially in symptomatic or postmenopausal women.
• Histology/Cytology Correlation: The Pap test helps correlate cell changes with subsequent biopsies, guiding further evaluation of cervical disease.
• Sample Adequacy: Only a cytologic assessment can reliably determine if enough cells from the transformation zone (where most cancers start) were collected. 
• Other Pathologies: Pap tests can also suggest other conditions in the gynecologic tract, such as inflammation or non-gynecologic malignancies.

4.  At-Home HPV Testing May Overdiagnose 

HPV infections are common and usually resolve spontaneously. If there is not a clear understanding of the implications of a positive result, widespread primary HPV testing might carry a significant risk of over-diagnosis and subsequent over-treatment.

For example, a positive HPV result (even for a transient infection that would naturally clear) necessitates follow-up tests and appointments. This can lead to anxiety, repeated testing and potential procedures like colposcopies and biopsies, even if there are no clinically significant lesions that lead to cancer. This burden on individuals, in terms of both psychological stress and physical discomfort, can be substantial. 

Secondly, the risk of persistent HPV infection leading to cervical cancer is much lower in younger individuals (under 25-30). In this age group, HPV testing is generally not recommended as a primary screening tool precisely because of the high rate of infection, the vast majority of which are harmless and transient, which could lead to a cascade of unnecessary interventions. One specific at-home HPV test has been approved for individuals aged 25 to 65, which means that this broader push for accessible primary HPV screening could, if not carefully managed, lead to testing in populations where it is less clinically beneficial and more prone to over-diagnosis.

5.  Lack of Additional Health Screenings and Next Steps 

It is crucial to remember that an at-home HPV doesn’t check for other important health issues that a regular doctor’s visit can catch, such as other types of gynecological cancers (ovarian, uterine), sexually transmitted infections, or other general health concerns. Relying solely on an at-home test might mean missing out on other vital health screenings.

Furthemore, understanding test results and next steps can be complex. While telehealth support is often provided, ensuring everyone understands their results and consistently follows up for further care is a big challenge. There’s a risk that people might get a positive result and not know what to do next, or simply not follow through, which could delay necessary treatment.

 

The Best Use of At-Home HPV testing 

While at-home HPV testing offers the potential for convenience and may increase screening participation, it’s essential to weigh these benefits against the significant concerns raised by many in the medical community. The potential for missed cancers, the limitations of certain HPV test types and the irreplaceable diagnostic value of the Pap test are critical considerations.

Many experts, including us at PathAdvantage, believe that co-testing (both HPV and the Pap test) or the Pap test with reflex HPV testing (secondary HPV testing after a Pap test or HPV test to confirm the diagnosis) remains the optimal approach for cervical cancer screening. This combined method offers the highest chance of detecting both early infections and cellular changes, ensuring comprehensive care and reducing the risk of missing treatable conditions. Ultimately, while technology can provide new options for care, ensuring the most thorough and effective screening for women’s health must remain the top priority.