Research report: Case Report: Superficial spreading squamous cell carcinoma of the cervix: a retrospective single-center case series and review of the literature

A retrospective study of seven women with superficially spreading squamous cell carcinoma of the cervix found that the tumors had an HPV-associated squamous phenotype and extended continuously along the mucosal lining of the uterus and, in selected cases, the vagina or fallopian tubes. The cervical lesions contained an invasive squamous cell carcinoma component with a maximum measured stromal invasion depth of 5 mm, while pelvic magnetic resonance imaging often showed only subtle uterine-cavity changes. All seven tumors showed block-type p16 expression in the cervical and extra-cervical components, and preoperative testing detected HPV16 in six women and HPV18 in one.

The findings describe a rare growth pattern within the cervical squamous cell carcinoma spectrum rather than a separately recognized cancer type, and the small series cannot establish a distinct prognosis or determine whether any particular treatment improves outcomes. The seven cases came from the pathology database of West China Second University Hospital, Sichuan University, covering diagnoses made from January 2010 through December 2025. Available hematoxylin and eosin-stained slides, pathology reports, clinical records, imaging findings, treatment information, recurrence status and follow-up records were reviewed retrospectively.

Cases were reassessed using the fifth edition of the 2020 World Health Organization Classification of Female Genital Tumors and staged under the 2018 FIGO system. To qualify as superficially spreading squamous cell carcinoma, abbreviated ss-SCC in the study, a lesion had to be centered in the cervix, show directly traceable continuity with at least one extra-cervical genital-tract site and grow predominantly within the mucosa. The investigators also required concordant morphology between involved sites and excluded independent primary tumors, metastatic neoplasms involving the cervix and spatially separate lesions without demonstrated continuity.

The final cohort included women aged 50 to 77 years, with a mean age of 60 years. Pathological reassessment showed that all seven cervical tumors contained invasive squamous cell carcinoma, although stromal invasion did not exceed 5 mm. Four also contained background cervical high-grade squamous intraepithelial lesions, termed HSIL under current WHO terminology.

In every case, the malignant squamous epithelium could be followed from the cervix into the endometrium. Selected cases also involved vaginal or fallopian-tube mucosa, while separate invasive foci at the vagina, endometrium, fallopian tube or ovary were documented independently because they were not the defining superficial spread. All seven tumors had exophytic or papillary architecture, creating morphological overlap with the papillary squamous cell carcinoma variant.

The researchers emphasized that papillary architecture alone is not diagnostic of ss-SCC. Its defining characteristic is instead a cervical-centered malignant lesion that can be anatomically traced as predominantly superficial mucosal extension across connected genital-tract surfaces, even when destructive stromal invasion is minimal. The clinical presentation varied.

Postmenopausal bleeding was reported by two patients, while one each had vaginal discharge with pyometra and contact bleeding. Three women were identified through routine Pap-smear screening. Preoperative HPV testing detected HPV16 in six cases and HPV18 in one, and all cervical and extra-cervical components showed strong, continuous nuclear and cytoplasmic p16 staining.

Block-type p16 supports an HPV-associated squamous phenotype, but the authors emphasized that it is neither site-specific nor proof that separated lesions are clonally related. Cervical origin in this series was assigned primarily through demonstrable anatomical continuity and concordant morphology. CK5/6 staining in one case supported squamous differentiation in a tubo-ovarian lesion, while HPV in situ hybridization or molecular clonality analysis would provide stronger evidence when continuity is uncertain.

Pelvic magnetic resonance imaging often understated the histological extent of the disease. Some scans showed only a small cervical mass, a fluid-distended endometrial cavity or a thin, uniformly enhancing layer along the endometrial surface, while occasional focal thickening was also present. Deep cervical stromal or myometrial invasion by nests of malignant cells was not identified on imaging in these cases.

A thin mucosal lesion can therefore remain radiologically occult, and histological sampling is needed to determine anatomical continuity and the presence of invasion. Limited biopsies or conization may not sample the upper genital tract and can consequently underestimate disease extent. The imaging observations in this cohort were descriptive rather than a validated diagnostic test, and their sensitivity was not formally quantified.

All seven patients underwent surgery. Three received radical hysterectomy and were assigned FIGO stage IB2 or IIA1, while four underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy for stage IA1 or IA2 disease. Five patients received postoperative adjuvant chemoradiotherapy.

During a median follow-up of 30 months, ranging from 11 to 54 months, two patients developed locoregional recurrence. Both were among the two patients who had not received initial adjuvant therapy; each later underwent salvage chemoradiotherapy and remained alive without evidence of disease at the last follow-up. All seven patients were alive, and no disease-related deaths occurred.

Because the cohort included only seven participants, two recurrences and no deaths, with substantially different treatments, the investigators performed no Kaplan–Meier survival analysis, subgroup comparisons or inferential testing. The observations therefore do not show whether initial chemoradiotherapy reduced recurrence, and they cannot establish an independent effect of treatment on outcome. The accompanying PubMed search covered literature from its inception through December 2025 and identified 25 eligible publications describing 44 patients.

Most were peri- or postmenopausal women, and vaginal bleeding and abnormal discharge were common presentations. The endometrium was the most frequently affected extra-cervical site, followed by the fallopian tubes. Published reports often used older terms such as carcinoma in situ or cervical intraepithelial neoplasia, which the researchers harmonized with current HSIL terminology.

Most patients with available follow-up were alive without evidence of disease, although one developed pulmonary metastasis. Treatments varied widely, follow-up information was often incomplete, and the reports were largely case reports and small series. The investigators therefore summarized results descriptively and did not perform pooled quantitative outcome analysis.

The investigators propose that ss-SCC be treated as a descriptive growth pattern within the HPV-associated cervical squamous cell carcinoma spectrum rather than as a separately staged entity. It is not recognized as a distinct category in the 2020 WHO classification, the 2018 FIGO system or the eighth edition of the AJCC manual. Established anatomical criteria therefore determine stage, while pathology reports should separately document the distribution of superficial extension, invasion depth at each involved site, lymphovascular space invasion, margin status and any non-contiguous invasive components.

This distinction is particularly important in the case with ovarian involvement: superficial spread can explain endometrial and tubal disease because those mucosal surfaces are anatomically continuous with the cervix, whereas the ovary lacks direct mucosal continuity. Ovarian disease and focal lymphovascular space invasion in that case raised the possibility of conventional dissemination coexisting with the superficial pattern, although the precise mechanism could not be established. The study also explored whether the predominance of older patients might reflect a hormone-related mechanism.

Investigators compared tumor-cell estrogen and progesterone receptor expression in the seven ss-SCC cases with five patients who had cervix-confined HSIL. Using the semiquantitative Allred scoring system, both groups showed reduced or absent nuclear expression, with no apparent qualitative difference. The comparison groups were small and unmatched, no formal statistical comparison was performed, and the results do not support estrogen or progesterone receptor loss as a specific driver, diagnostic feature or prognostic marker for ss-SCC.

Selected published studies have demonstrated clonal relationships between cervical and extra-cervical lesions through loss-of-heterozygosity or HPV-based analyses, but the present investigation did not perform molecular clonality testing across all involved sites. Overall, the available observations do not show that extensive superficial mucosal spread invariably indicates metastatic disease or poor prognosis, but the retrospective single-center design, small sample, heterogeneous treatment, limited follow-up and publication bias in the case literature leave those questions unresolved.

Subject of Research: Clinicopathological features and outcomes of superficially spreading cervical squamous cell carcinoma

Article Title: Case Report: Superficial spreading squamous cell carcinoma of the cervix: a retrospective single-center case series and review of the literature

Article References: Huang, H.-Q., Gong, F.-M., Xuan, Y., Wei, X.-X., & Zuo, X. (2026). Case Report: Superficial spreading squamous cell carcinoma of the cervix: a retrospective single-center case series and review of the literature. Frontiers in Oncology, 16, Article 1829547. https://doi.org/10.3389/fonc.2026.1829547

Image Credits: AI Generated

DOI: 10.3389/fonc.2026.1829547

Keywords: cervical cancer, HPV, squamous cell carcinoma, superficial spread, endometrial involvement, case series, p16, gynecologic oncology, pathology, case report, Case, Report