ctDNA analysis therefore represents a noninvasive substitute to tumor genome sequencing ( 7). Circulating tumor DNA (ctDNA) is a fraction of cell-free circulating DNA derived from tumor cells. More specifically, pretreatment squamous cell carcinoma antigen (SCCAg) levels are not validated as a predictive biomarker in metastatic SCCA ( 6). Distinguishing patients who will benefit from DCF and who will experience a sustained response after DCF completion may be clinically relevant, but cannot be achieved on the basis of imaging or the currently available biomarkers. Interestingly, some of the patients who completed the DCF course experienced rapid progression, while others remained progression-free after more than 2 years of follow-up. The proposed strategy was highly effective with a 1-year progression-free survival (PFS) rate of 47%, setting a new standard in this situation ( 5).

In this trial, DCF was administered for 5 months and was then discontinued, with no further chemotherapy until disease progression. In this context of metastatic or locally advanced recurrent SCCA, the Epitopes-HPV02 multicenter phase II trial assessed the efficacy of docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen as first-line palliative chemotherapy ( 5). In addition to 15% of patients with SCCA who are diagnosed with de novo metastatic disease, approximately 20% of patients with localized SCCA treated with concurrent chemoradiotherapy subsequently relapse, which may not be amenable to curative therapy ( 4). 2), especially HPV16, which is also implicated in oropharynx carcinoma and other anogenital cancers ( 3). Ninety percent of SCCA are associated with oncogenic human papillomavirus (HPV ref. Squamous cell carcinoma of the anal canal (SCCA) is a rare malignancy, but the incidence of SCCA is increasing in both men and women ( 1).

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