In February 2023, Seegene met with Marta del Pino at Eurogin, the leading international conference focused on human papillomavirus (HPV) and associated cancers, to discuss the value of HPV testing and genotyping in the new cervical cancer screening paradigm.
Del Pino is a gynecologist at the oncological gynecology unit of the Clinical Hospital of Barcelona and an associate professor at the University of Barcelona.
She is the vice president of the Spanish Association of Cervical Pathology and Colposcopy and a member of the International Federation of Cervical Pathology and Colposcopy as well as the HPV Action Network. In recent years, she has participated in the development of numerous national clinical guidelines and consensus documents related to the management of HPV-related lesions of the lower genital tract and screening strategies for cervical cancer prevention.
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. The World Health Organization estimates that more than 600,000 women globally are diagnosed with cervical cancer caused by HPV each year. There are many genotypes of HPV, and, while most infections cause no symptoms and improve without treatment within two years, 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, 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. These types are responsible for virtually all cases of cervical cancer, 70 percent of vaginal cancer, 40 percent of vulvar and penile cancers, 90 percent of anal cancer, and a variable percentage — between 40 percent to 75 percent, depending on the region — of head and neck cancer. The genotypes HPV16 and HPV18 are responsible for about 70 percent of cervical cancers. Other high-risk HPV types, including HPV 31, 33, 45, 52, and 58, together account for about 15 percent of cervical cancers.
Most infections will clear without medical intervention, but about one 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.
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.
How are Pap tests and HPV tests 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.
There are instances in which 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 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.
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.
Overall, the goals of these changes in screening guidelines are to improve the effectiveness of cervical cancer screening programs and to reduce the incidence of neoplasia by detecting precancerous lesions early and providing appropriate management, follow-up, and treatment.
Are there any other emerging diagnostic methods?
Other emerging HPV testing methods are being studied and developed. HPV mRNA testing detects the presence of the expression of some viral genes in cervical samples to identify women with active HPV infections that are more likely to develop to cervical lesions. The use of methylation analysis involves analyzing epigenetic modifications of some gene promotors in cervical cells associated with precancerous or cancerous cells. In addition, microRNAs might serve as biomarkers to distinguish between HPV-infected and uninfected individuals or to differentiate between different stages of HPV infection.
Additionally, researchers are exploring the use of tests and methods that can be performed by women to test themselves for HPV, such as 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.