Clinically Advanced Warty Invasive Squamous Cell Carcinoma of the Cervix with p16 Overexpression—Case Study and Literature Review

<b>Background and Clinical Significance:</b> Warty (condylomatous) squamous cell carcinoma (SCC) of the uterine cervix is a rare papillary variant of SCC, usually associated with good prognosis. <b>Case Presentation:</b> We report the clinical case of a postmenopausal woman with vaginal bleeding, anemia, and an enlarged, exophytic tumor mass protruding from the cervix. MRI showed a solid-necrotic cervical-uterine mass with invasion of bladder, rectum, both parametria, and the left ureter, with regional lymphadenopathy and FIGO IVA stage was established. Biopsies from the cervical tumor revealed invasive, well-differentiated SCC with conspicuous koilocytic atypia in superficial and deep nests, consistent with warty (condylomatous) SCC. Immunohistochemistry showed p16 overexpression, an intermediate nuclear proliferation rate, and a non-mutational pattern for p53 immunostaining. Radiotherapy was recommended but the patient's condition deteriorated rapidly and she died three months after initial diagnosis. Due to the rarity of this type of tumor, we conducted a search on PubMed, Scopus, and Web of Science from inception to 31 July 2025 and we identified ten reports available for evaluation. A total of 32 cases were identified, usually with FIGO stage I or II, mostly with low-risk HPV infection and with good prognosis. <b>Conclusions:</b> The advanced stage and limited tolerance for therapy in this case emphasize the importance of HPV vaccination and HPV-based screening to prevent late, non-curable presentations. Accurate distinction from condyloma acuminatum and verrucous or papillary SCC is clinically relevant because management and outcomes differ. Since some of the cases reported in the literature had a worse clinical course, with shorter disease-free survival and overall survival, including our case, further research is mandatory in the future to unravel those features which might predict a poor outcome.