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Author:
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Nicolás, Inmaculada; Marimon, Lorena; Barnadas, Esther; Saco, Adela; Rodríguez-Carunchio, Leonardo; Fusté, Pere; Martí, Cristina; Rodríguez Trujillo, Adriano; Torné Bladé, Aureli; Pino Saladrigues, Marta del; Ordi i Majà, Jaume
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Notes:
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Human papillomaviruses (HPV) are the causative agents of
virtually all cervical carcinomas. Nevertheless, a small
proportion of cervical cancer are negative for HPV, although the
significance of this finding remains unclear. We aimed to
provide insight into the differential clinico-pathological
characteristics of this unusual subset of HPV-negative cervical
cancer. We performed HPV-DNA detection using a highly sensitive
PCR test (SPF10) and p16 immunostaining in 214 cervical
carcinomas specimens from women treated at the Gynecological
Oncology Unit of the Hospital Clinic (Barcelona, Spain) from
2012 to 2015. The clinical and pathological characteristics,
including disease-free survival and overall survival, of
HPV-negative and -positive cervical carcinomas were compared.
Twenty-one out of 214 tumors (10%) were negative for HPV DNA.
HPV-negative tumors were more frequently of the non-squamous
type (9/21, 43% vs. 37/193, 19%;
p\xE2\x80\x89<\xE2\x80\x890.01) and showed negative p16
staining (9/21; 43% vs. 7/193; 4%;
p\xE2\x80\x89<\xE2\x80\x890.01). HPV-negative tumors were
more frequently diagnosed at advanced FIGO stage (19/21, 91% vs.
110/193, 57%; p\xE2\x80\x89<\xE2\x80\x890.01) and more
frequently had lymph node metastases (14/21, 67% vs. 69/193,
36%; p\xE2\x80\x89<\xE2\x80\x890.01). Patients with
HPV-negative cervical cancer had a significantly worse
disease-free survival (59.8 months, 95% confidence interval
32.0-87.6 vs. 132.2 months, 95% confidence interval 118.6-145.8;
p\xE2\x80\x89<\xE2\x80\x890.01) and overall survival (77.0
months, 95% confidence interval 47.2-106.8 vs. 153.8 months, 95%
confidence interval 142.0-165.6; p\xE2\x80\x89=\xE2\x80\x890.01)
than women with HPV-positive tumors. However, only advanced FIGO
stage and lymph node metastases remained associated with a poor
disease-free survival and overall survival on multivariate
analysis. In conclusion, our results suggest that a low
percentage of cervical cancer arise via an HPV-independent
pathway. These HPV-negative tumors are diagnosed at advanced
stages, show higher prevalence of lymph nodes metastases and
have an impaired prognosis. |
