The analytical model consists of a decision tree that simulates and compares the screening performance of each HPV testing strategy. The screening algorithm was developed based on the Portuguese legislation, the clinical consensus published by the Portuguese Society of Gynecology on cervical cancer screening, as well as on the opinion of a panel of clinical experts (Fig. 1) [2 , 17 ]. Details on the composition and the methodology of panel of clinical experts are available on the Additional file 1.

Cervical cancer screening decision tree

The analytical model simulates a cohort of 2,199,879 healthy women aged 25–60 years old. The hypothetical cohort moves between the model states, according to prespecified probabilities in each decision tree node, over a period of 2 years. These probabilities can be applied to estimate the number of women who followed each path within the screening algorithm and estimate the resulting costs and tests used.
According to clinical guidelines, women undergo routine screening for cervical cancer using the HPV test every 5 years. If the result of the HPV test is negative, women undergo routine screening again 5 years later. On the other hand, women testing positive for HPV serotypes 16/18 are referred for colposcopy, while women testing positive for other serotypes of HPV are referred for cytology. Women with a cytology showing ASCUS or worse are referred for colposcopy. Women with a normal result in the cytology are followed-up and re-tested for HPV after 12 months. Women re-testing negative return to routine screening and women re-testing positive are referred for colposcopy. Women with a colposcopy revealing conclusive results without high-grade histological lesions are followed-up and re-tested for HPV after 12 months (HPV-negative women return to routine screening and HPV-positive women undergo new colposcopy). Women with a colposcopy showing conclusive results with high-grade histological lesions undergo biopsy. Women undergo transformation zone (TZ) excision if they have a) inconclusive results in the colposcopy or b) a colposcopy with conclusive results without high-grade histological lesions after cytology High Grade Squamous Intraepithelial Lesion (HSIL). After biopsy results, women with CIN < 2 are followed-up and re-tested for HPV after 12 months (HPV-negative women return to routine screening and HPV-positive women undergo new colposcopy). Women with CIN ≥ 2 initiate treatment. Women with inconclusive results or conclusive results without high-grade histological lesions in the new colposcopy undergo TZ excision. Women with conclusive results with high-grade histological lesions in the new colposcopy repeat biopsy (Fig. 1). Both colposcopy and biopsy are assumed to be 100% sensitive and 100% specific [5 (link)].
Free full text: Click here