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Although the causal role of HPV in cervical cancer CC is accepted, controversial reports have been published about the prognostic significance of different genotypes. Our aim was to evaluate the HPV-status and its relationship with clinical-pathological variables and clinical outcome in invasive cervical cancer of Uruguayan women. Main prevalent genotypes were HPV16 (63.6%), HPV18 and HPV45 (8.3% each genotype), while other genotypes (HPV31, 33, 35, 39, 51, 52, 58, 66, 73 and one undetermined genotype) account for 12.4%, and in 8.3% HPV DNA could not be detected. With a mean follow-up of ten years, we found a significant correlation of overall survival with FIGO staging and lymph node metastasis. Relating to HPV, three prognostic groups were observed. The better clinical outcome was related to genotypes other than HPV16/18/45, while HPV16/18 genotypes belong to an intermediate risk group and the worse prognosis was related to HPV negative and HPV45. HPV independent tumors have been suggested as a different entity compared with virally driven ones. Improvement in knowledge of molecular pathogenesis could impact in CC patients care. In conclusion, worse prognosis was related to HPV negative and HPV45 related tumors. More research is warranted for better understanding molecular basis of virally driven or independent cervical cancer oncogenesis.