Human papillomavirus, p16INK4A, and Ki-67 in relation to clinicopathological variables and survival in primary carcinoma of the vagina

Abstract

Background:This study aimed to determine human papillomavirus (HPV) status and to investigate p16INK4A and Ki-67 expression and their correlation with clinical parameters and survival in women with primary carcinoma of the vagina (PCV).Methods:The presence of HPV DNA was evaluated by PCR. Genotyping was performed by Luminex in 68 short-term (⩽2 years) and long-term (⩾8 years) PCV survivors. p16INK4A and Ki-67 expression was evaluated by immunohistochemistry.Results:Human papillomavirus DNA was detected in 43% of patients, the majority (63%) of whom were HPV16 positive. High p16INK4A expression was significantly correlated with low histopathological grade (P=0.004), HPV positivity (P=0.032), and long-term survival (P=0.045). High Ki-67 expression was negatively correlated with histopathological grade (P<0.001) and tumour size (P=0.047). There was an association between HPV positivity and low histopathological grade, but not between HPV positivity and survival.Conclusion:High p16INK4A expression was associated with long-term survival, but the only independent predictors for survival were tumour size and histopathological grade. Our results indicate that p16INK4A and Ki-67 expression might be useful in tumour grading, and that it might be possible to use p16INK4A expression as a marker for HPV positivity, but this has to be further elucidated.

Human papillomavirus and p16 in squamous cell carcinoma and intraepithelial neoplasia of the vagina

“…11,14 For vaginal cancer, however, studies reporting data on p16 are limited and often based on small numbers of cases. In Hellman et al, 42 18 out of 19 HPV positive tumors were also p16 positive, and in Alemany et al, 55 96 out of 110 HPV positive tumors were also p16 positive. Pooling the results of these studies, we found p16 positivity in 89% of HPV positive vaginal cancers, suggesting a considerable proportion of HPV positive cancers to be HPV-induced.…”

“…54 The majority of studies (n = 20) used a PCR-based method for HPV DNA detection, whereas seven studies used HC2. 32,33,43,45,47,49,51 Among the studies using a PCR-based test, 12 used a single set of consensus primers, 27,28,31,36,39,40,42,48,[52][53][54][55] three used a combination of consensus primers, 30,35,38 two used combinations of typespecific and consensus primers, 44,46 two used type-specific primers alone, 26,37 and one study used in house primers. 41 All studies examining p16 positivity (n = 6) used immunohistochemistry (IHC) to detect overexpression of the p16 protein.…”

“…Five studies used the CINtec ® Histology Kit (Ventana Medical Systems, Inc.) with p16 antibody (clone E6H4) 34,38,42,50,55 and one study used another commercially available p16 antibody (clone G175-405, BD Pharmingen). 29 Various cut-offs for p16 positivity were applied in the individual studies: diffuse staining of ≥25% 34,38,42,55 or ≥ 10% 29 of the tumor, or any staining intensity above negative control (i.e., ≥1% of cells with staining intensity scored ≥1 on a scale from 0 to 3). 50…”

Interaction of HPV with vaginal ecosystem in vaginal and cervical carcinogenesis

“…), on gynecologic infections, on the assessment of the vaginal ecosystem (pH, lactobacillus), on cytopathologic diagnosis (atypical pavimentous cells of undetermined significance; low grade squamous intraepithelial lesions -LSIL; high grade squamous intraepithelial lesions -HSIL, Atypical glandular cells -AGC; Cervical Intraepithelial Neoplasia I -CINI; and Cervical Intraepithelial Neoplasia I and II -CINII/III), on molecular diagnosis (HPV, viral load, HSV, CMV, Chlamydia trachomatis, Mycoplasma, Ureaplasma, Neisseria gonorrhoeae) and on the Immunohistochemical study (p16 e Ki-67) of dysplasia components (7)(8)(9) . …”

Is differential expression of p16INK4a based on the classification of uterine smooth muscle tumors associated with a different prognosis? A meta-analysis

“…The authors of previous studies have reported the diagnostic and prognostic value of overexpressed p16INK4a protein in various cancers and premalignant lesions (Sano et al, 1998;Bu et al, 2014;Huang et al, 2014;Cao et al, 2016). Although p16INK4aoverexpression might be used as a surrogate marker for human papilloma virus (HPV) in cervical and vaginal carcinoma, its overexpression in other carcinomas is not necessarily related to HPV (Hellman et al, 2014). However, its diagnostic and prognostic role in USMTs remains ambiguous (Atkins et al, 2008;Mills et al, 2013).…”