The Clinical Importance of HPV Genotyping

Gynecologist in blue gloves is taking smear analysis for research detect sexually transmitted diseases and HPV detectionAt least 80% of all sexually active women and 90% of all sexually active men will encounter an HPV virus at some point in their lives, making human papillomavirus a serious public health issue. Most HPV infections are cleared by the individual’s immune system, however high-risk HPV infections that persist can cause cancer.

To reduce the overall prevalence of HPV infections and limit the number of cancers associated with high-risk strains, it is essential to develop better prevention strategies and treatment methods. Currently, genotyping offers the greatest promise for managing the impact of HPV on human health.

Understanding HPV and Its Impact

HPV is a group of more than 150 related viruses, about 40 of which affect the genitals. What makes HPV so difficult to prevent and treat is the possibility for the same individual to be infected by multiple strains. Even more worrying, out of more than 150 HPV strains, at least 14 of these HPV viruses are classified as high-risk types.

Although it’s important to detect and treat all types of HPV, strains 16 and 18 have been linked to more than two-thirds of all cervical cancer cases.1

High-Risk HPV Types

HPV types are considered high-risk when they contain oncogenes that disrupt normal cell cycle regulation and promote proliferation. These cellular changes can lead to precancerous lesions, which, if left untreated, can progress to cancer. Among high-risk HPV types, HPV 16 and HPV 18 are the most common and are responsible for approximately 70% of cervical cancer cases. Other high-risk HPV types include: HPV 31, HPV 33, HPV 35, HPV 39, HPV 45, HPV 51, HPV 52, HPV 56, HPV 58, HPV 59, and HPV 68

These high-risk HPV types can cause various cancers, including cervical cancer, oropharyngeal cancer, anal cancer, vaginal and penile cancers.

Low-Risk HPV Types

Genotypes that are not associated with cancer are categorized as low-risk HPV Types, like HPV 6 and HPV 11. Despite a low risk of cancer, these types can still cause significant conditions such as genital warts and respiratory papillomatosis, leading to healthcare challenges, and testing for them is still important.

Diving Deeper: Detection of HPV Types

Genotyping is better than simple detection because it identifies subtle differences in virus types, enabling researchers to develop targeted treatments or estimate an individual’s risk of developing cancer and other diseases. Genotyping also allows clinicians to better predict patient outcomes, improving their decision-making capabilities.2

For the detection of HPV genotypes by PCR, a mix of consensus primers and type-specific primer sets are used to amplify HPV viral DNA to identify high-risk genotypes. As a result, PCR makes it possible to distinguish high-risk HPV 16 from low-risk HPV 4.3 Therefore, the process plays an important role in assessing an individual’s risk of cervical cancer.

Testing provides several advantages, including:

  • Correct Diagnosis: Precise identification of HPV Types for high-risk is critical to identify cancer precursors or early cancer diagnosis. Identifying not only high-risk, but also genital wart causing low-risk types, are critical in managing and treating the condition.
  • Differentiating between high-risk and low-risk types: Symptoms alone may not be enough to determine whether an HPV infection is high-risk or low-risk. Testing can identify the type, which can then inform the management plan and surveillance for cancer precursors.

Through testing, public health officials can understand the distribution of low-risk vs. high-risk HPV types and monitor the impact of vaccination programs as well.

The Science of HPV Detection

The U.S. Preventive Services Task Force recommends cervical cancer screening for all women between the ages of 21 and 65. Traditionally, Pap smears have been used to identify cervical dysplasia associated with HPV.4 Pap smears identify only associated symptoms and don’t detect HPV, however.

Polymerase chain reaction (PCR) revolutionized the science of HPV detection, allowing laboratory professionals to use consensus primers to amplify many HPV genotypes at once. PCR detection techniques have high levels of specificity and sensitivity, making them superior for cervical cancer screening when compared to traditional cervical cytology tests.

The Pap Smear

The Pap smear, also known as a Pap test, is the most common screening method for cervical cancer. Its popularity is mainly due to the following factors:

  • Simplicity: The Pap smear is a relatively simple procedure to perform. It requires minimal equipment and can be done in a doctor’s office.
  • Accessibility: Most healthcare professionals are trained to perform Pap smears, which makes the test broadly accessible to women around the world.
  • Positive track record: Since its introduction in the 1940s, the Pap smear has a proven track record of effectiveness and plentiful data on its limitations and best practices.

During a pap test, cells are collected from the cervix’s surface with a small brush or spatula, then smeared on a glass slide and sent to a laboratory for analysis. A cytotechnologist examines the cells to identify any abnormalities.

Pap Smear vs. PCR Testing

While the Pap smear remains the standard screening method for cervical cancer, PCR testing is particularly well-suited to detecting HPV. Some key benefits of PCR testing are:

  • Sensitivity and specificity: PCR tests are better suited for detecting HPV due to increased sensitivity and specificity.
  • Early detection: Because high-risk HPV types are linked to cervical cancer, detecting the presence of a virus can identify risks earlier than cellular changes might be detected on a Pap smear.

However, PCR testing is used primarily to detect the presence of HPV, it does not replace the need for Pap smear in detecting any cellular abnormalities. In some cases, such as women between the ages of 30 and 65, a combination of Pap smear and HPV testing via PCR is preferable.

Clinical Importance of Detecting HPV Types

PCR and genotyping have not only revolutionized laboratory science, but they’ve also transformed patient care from diagnosis to treatment. Identifying the specific strain of HPV present in a sample helps determine a patient’s risk of developing HPV-related cancer, enabling clinicians to make better decisions regarding follow-up testing.

Medical professionals also use genotyping results to make recommendations regarding vaccination and other preventive measures, especially in women who have been diagnosed with persistent infections.5

Identifying the correct HPV strain also makes it easier to develop effective vaccines. Researchers use genotyping to develop and evaluate trials for vaccines specifically targeting individuals with high-risk HPV strains. It may even be possible to use genotyping to determine how an individual is likely to respond to vaccination.6

Improving Global Health

Detecting HPV subtypes has important implications for global health, as it has the potential to improve patient outcomes and enable clinicians to develop more precise treatment methods. Women may also benefit from the use of PCR to identify the organisms responsible for vaginosis and vaginitis, both of which cause inflammation, discomfort, and other bothersome symptoms.

References

  1. Sofiani VH, Veisi P, Rukerd MRZ, Ghazi R, Nakhaie M. The complexity of human papilloma virus in cancers: a narrative review. Infectious Agents and Cancer. 2023;18(1). doi:https://doi.org/10.1186/s13027-023-00488-w
  2. Inkman MJ, Jayachandran K, Ellis TM, et al. HPV-EM: an accurate HPV detection and genotyping EM algorithm. Scientific Reports. 2020;10(1):14340. doi:https://doi.org/10.1038/s41598-020-71300-7
  3. Choi YJ, Park JS. Clinical significance of human papillomavirus genotyping. Journal of Gynecologic Oncology. 2016;27(2). doi:https://doi.org/10.3802/jgo.2016.27.e21
  4. Abreu ALP, Souza RP, Gimenes F, Consolaro MEL. A review of methods for detecting human Papillomavirus infection. Virology Journal. 2012;9(1):262. doi:https://doi.org/10.1186/1743-422x-9-262
  5. Jentschke M, Soergel P, Hillemanns P. Importance of HPV Genotyping for the Screening, Therapy and Management of Cervical Neoplasias. Geburtshilfe und Frauenheilkunde. 2012;72(6):507-512. doi:https://doi.org/10.1055/s-0032-1314959
  6. Castiblanco J, Anaya JM. Genetics and Vaccines in the Era of Personalized Medicine. Current Genomics. 2015;16(1):47-59. doi:https://doi.org/10.2174/1389202916666141223220551
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