What is genotyping?
In cervical screening, HPV genotyping refers to testing that identifies which type of human papillomavirus (HPV) is present in a sample.
There are over 100 HPV types, but only a small number are considered high-risk for cervical cancer. Genotyping helps determine a woman’s risk level and guides follow-up and referral decisions.
A negative HPV test today does not guarantee future risk. HPV testing is more sensitive than cytology screening. Sensitivity refers to the ability of a test to accurately detect an underlying condition. Due to its higher sensitivity, HPV testing is more effective at detecting precancerous lesions and cervical cancer.
However, it is important to note that while HPV testing is more sensitive, it is less specific. This means it may detect women with transient HPV infections that might not have caused any cervical cell changes. Some women will clear HPV infections by themselves without any treatment. Therefore, a triage cytology test is necessary to distinguish between transient HPV infection, which is less likely to cause harm, and persistent/high risk HPV, which poses a higher risk of leading to precancerous changes or cervical cancer. That is why all of those with HPV infection have a reflex cytology test performed in CervicalCheck. This helps to identify who needs to go to colposcopy and helps to reduce the harms of cervical screening, including over-investigation and over-treatment of HPV infections.
Some countries use HPV genotyping instead of, or with, cytology testing for triage. HPV genotyping is another way of identifying who is most at risk of developing cervical disease and who needs to be seen in colposcopy early.
Types of HPV genotyping used in cervical screening
Partial genotyping (used in some cervical screening programmes, for example, in the Netherlands and Australia)
This method identifies:
- HPV 16
- HPV 18
- All other high-risk types grouped together
Why?
HPV 16 and 18 cause around 70% of cervical cancers, so detecting them separately helps prioritise faster referral.
Full Genotyping
This identifies each high-risk HPV type individually, such as HPV 31, 33, 35, 45, 52, 58, etc.
This provides more detailed risk information but this author does not know of any national screening programme that does this. It is expensive and has not yet shown clear benefit for large population-level screening pathways
HPV mRNA testing
Instead of detecting viral DNA, mRNA tests look for viral gene activity, which may indicate a higher chance of progression. Some systems use this as an add-on, but it is not standard in Ireland’s national screening pathways.
Limitations of genotyping in cervical screening
- HPV positivity does not mean cancer.
Many people clear HPV on their own within 1–2 years. Genotyping shows risk, not disease.
- Partial genotyping may miss nuances
Grouping “other high-risk types” together can overestimate risk for some women and underestimate differences among less common but still relevant types
- Anxiety and over-referral
A positive HPV result especially without abnormal cells can cause worry, even though most cases resolve naturally.
- Not all high-risk types behave the same
Even with extended genotyping, we still cannot perfectly predict who will clear the infection and who will progress to high-grade changes
- HPV testing does not screen for all gynaecological cancer
It only relates to cervical cancer risk. It does not detect any of the other 4 gynaecological cancers, ovarian, uterine, vulval or vaginal cancers. This is a limitation of cervical screening in general rather than genotyping in particular.
The CervicalCheck Team regularly reviews the evidence for the utility of HPV genotype information for cervical screening. If there is sufficient evidence that HPV genotyping is a better triage test, then they will ask the National Screening Advisory Committee to make a recommendation on how best to incorporate HPV genotyping into CervicalCheck.