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In February 2023, Seegene met with Dr. Marta del Pino at Eurogin, the leading international conference focused on human papilloma virus (HPV) and associated cancers, to discuss the value of HPV testing and genotyping in the new cervical cancer screening paradigm. Read on to learn more about this topic.
How common is HPV?
According to the US Centers for Disease Control and Prevention, HPV is the most common sexually transmitted infection, with data showing that nearly all sexually active people will get at least one type of HPV at some point in their lives.1 Globally, it is estimated that more than 600,000 women are diagnosed with cervical cancer caused by HPV each year.2 There are many genotypes of HPV, and while most infections cause no symptoms and improve without treatment within two years3, some types of HPV can cause health problems such as genital warts and cancer.
How often does HPV lead to cancer?
There are over 200 types of HPV. Each type is classified as either low-risk or high-risk depending on its likelihood of leading to cancer,4 the latter being responsible for causing cancer over time. There are around 14 high-risk HPV types including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68.5 These types are responsible for virtually all cases of cervical cancer, 70% of vaginal cancer, 40% of vulvar and penile cancers, 90% of anal cancer; and a variable percentage, between 40% to 75% depending on the region, of the head and neck cancer.6 Among the high-risk HPV, the genotypes HPV16 and HPV18 are responsible for about 70% of cervical cancers.7 Other high risk HPV types, including HPV 31, 33, 45, 52, and 58 together account for about 15% of cervical cancers.
Most infections will clear without medical intervention, but about 1 in 10 infections caused by high-risk HPV types may become persistent infections that can cause pre-cancerous lesions. When these premalignant lesions are not detected early and treated, they may progress to cancer. This process, from infection to cancer, usually takes 15 to 20 years.2
Among all HPV-related neoplasias, cervical cancer can be prevented through primary prevention (vaccination) or secondary prevention (screening programs). Indeed, a well-proven way to prevent cervical cancer is to get regular screenings with an HPV test and/or Pap test (also called a Pap smear or cervical cytology) to detect and treat abnormal cell changes early on.8
How are Pap test and HPV test different?
The Pap test looks for abnormal cells from precancerous lesions, cell changes that may turn into cervical cancer if they are not treated appropriately. It gives us information about whether a woman with an infection is at risk of underlying premalignant lesions. The HPV test checks for the presence of high-risk HPV types in cervical cells. It is more sensitive than a Pap test for detecting women at risk of developing lesions but is also less specific.9
There are instances where HPV DNA genotyping can be useful to identify the specific type of HPV that is present in the sample. This test can distinguish between different types of high-risk HPV that may have different levels of premalignant lesions or cancer risks. Extended HPV genotype provides valuable information about risk stratification, enabling the identification of both women at a high risk and at a low risk of developing premalignancies. Therefore, knowing the specific type of HPV can help determine the appropriate management and follow-up care.
What are the current cervical cancer screening guidelines in Europe? Are there any noticeable shifts in screening guidelines?
There have been some noticeable shifts in cervical cancer screening guidelines across Europe in recent years. The guidelines from different countries of the European Union recommend that women aged 25 to 64 undergo regular cervical cancer screening using HPV testing. The recommended frequency of screening varies by country, but it typically ranges from every three to five years. Current guidelines recommend performing a cytology on HPV-positive women to identify those at higher risk of lesions which would benefit from either further explorations or closer follow-ups.
Several countries, including Portugal, the Netherlands, and the United Kingdom, have shifted to using HPV testing as the primary screening method, with cervical cytology used as a secondary test in cases where HPV is detected.10
Another shift has been the extension of the screening age range in some countries. Countries, such as Switzerland have extended the upper age limit for screening from 65 to 70, while others, such as Germany and Austria, have lowered the lower age limit to 20.9
Overall, the goal of these changes in screening guidelines is to improve the effectiveness of cervical cancer screening programs and to reduce the incidence of neoplasia by detecting precancerous lesions early, providing appropriate management, follow-up and treatment.
Are there any other emerging diagnostic methods?
There are other emerging HPV testing methods that are being studied and developed. HPV mRNA testing detects the presence of some viral genes expression in cervical samples identifying women with active HPV infections that are more likely to develop to cervical lesions.11 The use of methylation analysis involves analyzing epigenetics modifications of some gene promotors in cervical cells associated with precancerous or cancerous cells.12 In addition, microRNAs might serve as biomarkers to distinguish between HPV-infected and uninfected individuals or to differentiate between different stages of HPV infection.13
On the other hand, researchers are exploring the use of tests and methods to detect HPV that can be performed by women themselves, such as the analysis of self-collected vaginal swabs or urine samples. These methods could potentially make HPV testing more accessible and convenient for women who are unable or unwilling to undergo screening in outpatient clinics or the hospital.
Researchers will continue to develop optimal screening strategies to improve its accuracy and accessibility and help to reach cervical cancer elimination worldwide as promoted by the World Health Organization.
References
- Centers for Disease Control and Prevention. HPV Infection. https://www.cdc.gov/hpv/parents/about-hpv.html
2. WHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention. 2nd ed. Geneva: World Health Organization; 2021.
3. World Health Organization. Human papillomavirus (HPV). 5 April 2017. https://www.who.int/europe/news-room/fact-sheets/item/human-papillomavirus-(hpv)
4. World Health Organization. Questions and Answers about Human Papilloma Virus. January 2020. https://www.euro.who.int/__data/assets/pdf_file/0003/427017/WHO-HPV-QA.pdf
5. National Cancer Institute. HPV and Cancer. 31 January, 2023. https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/hpv-and-cancer
6. Tulay P, Serakinci N. The role of human papillomaviruses in cancer progression. Journal of Cancer Metastasis and Treatment. 2016; 2:201-13. http://dx.doi.org/10.20517/2394-4722.2015.67
7. Meites E, Gee J, Unger E, Markowitz L. Human Papillomavirus. Centers for Disease Control and Prevention. https://www.cdc.gov/vaccines/pubs/pinkbook/hpv.html#hpv
8. Zhu Y, Feldman S, Leung SOA, Creer MH, Warrick J, Williams N, Mastoridese S. AACC guidance document on cervical cancer detection: screening, surveillance, and diagnosis. [Epub] J Appl Lab Med March 6, 2023, as doi: 10.1093/jalm/jfac142.
9. Perkins RB, Guido RL, Saraiya M, Sawaya GF, Wentzensen N, Schiffman M, Feldman S. Summary of Current Guidelines for Cervical Cancer Screening and Management of Abnormal Test Results: 2016-2020. J Womens Health (Larchmt). 2021 January;30(1):5-13. doi: 10.1089/jwh.2020.8918. PMID: 33464997; PMCID: PMC8020523.
10. World Health Organization. Cervical Cancer Country Profiles. 2021. https://cdn.who.int/media/docs/default-source/ncds/ncd-surveillance/cxca/cxca-profiles/cxca-profiles-en.pdf?sfvrsn=d65f786_23&download=true
11. Arbyn M, Simon M, Sanjose S. Accuracy and effectiveness of HPV mRNA testing in cervical cancer screening: a systematic review and meta-analysis. The Lancet Oncology. 2022 June; 23(7): 950-960. https://doi.org/10.1016/S1470-2045(22)00294-7
12. Hillyar C, Kanabar S, Pufal K. A systematic review and meta-analysis of the diagnostic effectiveness of human papillomavirus methylation biomarkers for detection of cervical cancer. Epigenomics. 2022 September. https://doi.org/10.2217/epi-2022-0160
13. Nagandla K, Lin KH, Chitra E, Jamli MFBM. Role of microRNAs as biomarkers of cervical carcinogenesis: a systematic review. Obstet Gynecol Sci. 2021 Sep;64(5):419-436. doi: 10.5468/ogs.21123. Epub 2021 Aug 13. PMID: 34384196; PMCID: PMC8458608.
