Is human papilloma virus viral load a clinically useful predictive marker: a longitudinal study

Human papilloma viruses (HPV) are a group of more than 100 related viruses and they are one of the primary causes of cervical cancer in women. These are divided into low risk and high risk types based on their ability to cause cancer. There is need to distinguish between those women who test positive for high risk (HR) human papilloma virus (HPV) types and are likely to acquire cervical neoplasia and those women who test positive for HR-HPV but who are not at increase risk. This distinction would require one to study biomarkers. One such biomarker is HPV viral load. It has been observed that in women who are positive for HR HPV types, cytological abnormalities were found to be positively associated with HPV viral load. However, the relationship between HPV viral load and cervical neoplasia is not clear and seems to be complex. In this study, the authors have tried to determine this relationship by measuring viral load of HPV16 and HPV18, HR-HPV types in serial samples taken during the follow up of a group of young women who were recruited soon after they first had sexual intercourse.

Results:

Viral load waxes and wanes during follow up: In the study, 118 women who had an incident of HPV infection (HPV16 or HPV18) as detected by GP5+/GP6+ system and who provided at least three samples for qPCR during follow-up, at least one of which was positive, were studied. Sixty women were tested positive for HPV16 using qPCR. Of these 60, 41 tested positive in all three samples; 10 in two; and 9 in one. Fifty eight women were tested positive for HPV18. Of these 58, 39 were positive in all three samples, 5 in two and 14 in one. In the 60 women with HPV16 infection, median copy number was 7.7 in their first qPCR positive sample and 7.8 in their last positive sample. In the 58 women with HPV18 infection, median copy number was 2.3 in their first qPCR positive sample and 2.4 in their last positive sample. Viral load appeared to increase and decrease during follow up. Among 43 women with HPV16 infection and among 35 women with HPV18 infection, maximum viral load observed during follow up was found to be increased than that detected in the first qPCR positive sample and it was greater than that detected in the last qPCR positive sample in 37 of these women with HPV-16 infection and 32 with HPV18 infection.

Increase viral load is associated with an increase risk of acquiring an incident cervical cytological abnormality: There was no significant difference in the maximum HPV16 viral load or the maximum HPV18 viral load between women who subsequently acquired an incident cytological abnormality and those who did not. However, when viral load was modelled as a log10-transformed continuous covariate, controlling for whether or not a woman had ever tested positive for the relevant type using qPCR, it was observed that a 10 fold increase in HPV viral load was associated with a significantly increased risk of acquiring an incident cervical cytopathological abnormality in women with HPV16 or HPv18 infection.

 

Conclusions: Thus, the study concludes that while large relative increase in the viral load was associated with an increase risk of cytological abnormality, a single measurement of viral load done at an intermediate point during the natural history of HPV infection, does not reliably predict the risk of acquiring cervical neoplasia.

 

Source: Constandinou-Williams C, Collins SI, Roberts S, Young LS, Woodman CB, Murray

PG. Is human papillomavirus viral load a clinically useful predictive marker? A

longitudinal study. Cancer Epidemiol Biomarkers Prev. 2010 Mar;19(3):832-7.