Reading the virus: Virologists search for a clearer signal after an HPV test
- Beth Amato
Can investigating whether molecular patterns in high-risk HPV help identify women whose infections are associated with significant cervical changes?
A positive high-risk human papillomavirus (HPV) result identifies a virus with the potential to cause cervical cancer. It does not mean that a woman has cancer, or that she will develop it. Nor can the result show whether the infection has begun causing clinically significant changes in the cervix.
Nigerian virologist Dr Ijeoma Ifeorah is spending part of an Africa Research Excellence Fund Research Development Fellowship at Wits investigating whether the virus itself contains a more useful clue.
Her project examines mutations and DNA methylation patterns in high-risk HPV types 16 and 18 from Nigerian women living with HIV and with different grades of cervical lesions. These two HPV types are responsible for around three-quarters of cervical cancers.
If particular molecular patterns are consistently associated with more significant cervical changes, they could eventually contribute to a second-level test performed on the same cervical sample already collected for HPV testing. Because this is early-stage research, useful markers would need to pass several stages of validation.
The question after a positive result
Persistent infection with high-risk HPV causes almost all cervical cancers, but most HPV infections clear naturally without treatment. Risk increases when the virus persists and begins altering cervical cells.
HPV testing is increasingly important because it can detect high-risk forms of the virus before cancer develops. The sample may be collected by a healthcare worker or by the woman herself. The World Health Organization says self-collected samples have been shown to be as reliable as samples collected by healthcare providers.
But greater access to testing also makes the next question more pressing: what should happen when the result is positive?
Women who test positive may require a second level of assessment, known as triage, to determine whether there are abnormal cervical changes requiring closer investigation or treatment. Depending on the setting, this can include cytology, commonly known as a Pap smear, visual inspection of the cervix or colposcopy.
These methods remain important, but they may depend on trained specialists, good-quality specimens, equipment and, in some cases, another clinic visit. In health systems with limited specialist capacity, each additional step can strain services and increase the chance that a woman will be lost to follow-up.
Ifeorah is investigating whether a molecular test could eventually add another layer of information. It would not replace the initial HPV test. Instead, it would look more closely at the virus detected in the sample for signs associated with clinically significant cervical changes.
A ‘red ribbon’ on the virus
Ifeorah describes a biomarker as a “red ribbon” that makes one infection stand out from another.
Part of her work examines mutations in the HPV genome. She is also studying DNA methylation: chemical tags attached to DNA that can influence how genes behave. Certain methylation patterns may become more common as persistent HPV infection is associated with abnormal cellular change.
The study will compare these patterns in HPV16 and HPV18 samples from Nigerian women living with HIV who have different grades of cervical lesions. If a particular pattern repeatedly appears alongside more significant lesions, it could become a candidate biomarker for further study.
The distinction is important. The project is looking for patterns associated with cervical lesion grade. It is not yet a diagnostic test, and it cannot currently predict what will happen to an individual woman.
During the fellowship, Ifeorah is gaining experience in next-generation sequencing, including methylation analysis using Oxford Nanopore sequencing, as well as bioinformatics methods needed to interpret the resulting data.
Why women living with HIV matter
Women living with HIV are six times more likely to develop cervical cancer than women without HIV. A weakened immune response can make it more difficult to clear HPV, allowing an infection and related cervical disease to persist.
This makes reliable screening and triage particularly important. WHO recommends that women living with HIV begin cervical screening earlier and undergo screening more frequently than the general population.
Yet data on mutations and DNA methylation patterns in HPV16 and HPV18 remain limited in Nigeria. Ifeorah’s project is intended to begin addressing that evidence gap using samples from Nigerian women rather than assuming that molecular patterns identified elsewhere will necessarily provide the same information.
Building the expertise in Nigeria
Ifeorah is a Senior Lecturer at the University of Nigeria and a Research Associate at the IVAN Research Institute in Enugu. Her fellowship is hosted at the Wits Infectious Disease and Oncology Research Institute and the Antiviral Gene Therapy Research Unit.
She is working under the mentorship of Professor Patrick Arbuthnot, Professor Betty Maepa and Dr Kuben Naidoo, gaining practical experience in sequencing, methylation analysis and bioinformatics. She plans to take these skills back to Nigeria while developing a longer-term research partnership with Wits.