Risk assessment to guide the prevention of cervical cancer

Risk of cervical precancer and results of screening and clinical management for cervical cancer prevention

A graphical representation of the risk of cervical precancer at different stages and results of screening and clinical management for cervical cancer prevention. The risks for each stage and result are approximate risks for CIN3 within a screening interval. The axis to the right of the figure represents increasing risk, from nearly 0% (blue) to 100% (red), of cervical precancer on a log scale. Each stage of screening and clinical management is represented by a different pattern, with the arrows at the bottom indicating the sequence of the stages. Number sign indicates that less than half of the cases of CIN2 on biopsy are subsequently diagnosed as CIN3 on excisional tissue (precancer). Dagger indicates time within a screening interval. Asterisk indicates test results at the next follow-up visit (6 months or longer).

Castle. Risk assessment for prevention of cervical cancer. AJOG 2007.

Cumulative incidence of precancer

The figure shows the cumulative incidence of precancer (CIN3) and cancer (CIN3 or greater) by HPV status and illustrates two aforementioned outlined principles: risk stratification and contextual use of a test. A positive test for carcinogenic HPV in women 30 years old and older even with negative cytology can identify those women at risk of precancer and cancer. More importantly, those who tested negative are at an extremely low risk over many years¹² and should not be screened again for several years; the current screening recommendation is that women who are cytology and carcinogenic HPV negative should not be rescreened before 3 years.⁸ If the positive carcinogenic HPV test is then triaged using HPV16 and HPV18 detection, there is further risk stratification, with HPV16-positive or HPV18-positive women being at an extremely high risk of developing precancer or cancer.⁹ In fact, this risk was greater than the risk observed for women with LSIL, for whom colposcopy is recommended. Thus, when a validated HPV genotyping assay becomes available, colposcopy for HPV16-positive or HPV18-positive, cytology-negative women may be warranted. However, the appropriate management for HPV16-negative/HPV18-negative, carcinogenic HPV-positive, cytology-negative women becomes less clear because the absolute risk is low, yet these women still remain at risk for the 30% of the cancer not caused by HPV16 and HPV18. This clinical conundrum will become more common to screening of women 10-15 years after they have received vaccination against HPV16 and HPV18 infections.³⁰ Thus, the risk of cervical precancer and cancer among women who test positive for carcinogenic HPV will differ between those who have and have not been previously vaccinated. (n.b., the X-axis does not represent continuous time and the time points represent midpoints within a follow-up time period. Follow-up time was crudely divided into an initial period of 0-9 months (Papanicolaou smears that were rapidly repeated, presumably prompted by a previous cytologic abnormality or suspicious symptoms), followed by yearly intervals for a total time of 122 months. These intervals roughly paralleled the intervals at which women returned for annual smears⁹).

Castle. Risk assessment for prevention of cervical cancer. AJOG 2007.