Performance of p16/Ki67 Immunostaining for Triage of Elderly Women with Atypical Squamous Cells of Undetermined Significance

Bruno, Maria Teresa; Guaita, Arianna; Boemi, Sara; Mazza, Gabriele; Sudano, Maria Chiara; Palumbo, Marco

doi:10.3390/jcm12103400

Cited by 4 publications

(6 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The atrophy changes on squamous epithelium makes the Pap test less precisive and speci c in detection of HISL [18,19] . Recent studies found that P16/Ki67 double-stained cytology performed high pro les for CIN2 + in postmenopausal women cytologically reported with ASC-US [20] . As misinterpretation of HSIL + would not only bring heavy psychological pressure to women, but lead to unnecessary biopsies in subsequent colposcopy, the performance of P16 immunocytochemical stain in facilitation of the cytology interpretation for women at age of 50 or above is worth of address in its clinical application.…”

Section: Discussionmentioning

confidence: 98%

Performance of P16 INK4a immunocytochemical stain in facilitating cytology interpretation of HSIL for women aged 50 and above

Hou,

Du,

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Few articles have focused on cytological misinterpretation of the high-grade squamous intraepithelial lesion (HSIL) in older women. Due to estrogen deficiency, cervical epithelial cells in postmenopausal women tend to show atrophic change that looks like HISL, resulting in a higher rate of cytological misinterpretation. P16INK4a immunocytochemical staining (P16-cytology) can effectively differentiate diseased cells from normal atrophic ones with less dependence on cell morphology. Objective To evaluate the performance of P16-cytology in differential analysis of cytology high-grade squamous intraepithelial lesions and benign atrophy in women aged 50 years and above. Methods Included in this analysis were the women who were positive of hr-HPV in a cervical cancer screening project in central China and returned back for triage, with complete data of primary hr-HPV test, Liquid-based cytology, P16 immuno-stained cytology, and ptholosgy diagnosis. Included patients were divided into ≥ 50 (1,127 cases) and < 50 years (1,430 cases) of age groups. The accuracy of LBC in the diagnosis of ≥ HSIL was compared between the two groups, and detailed analysis was conducted to demonstrate how many cases with cytology ≥ HISL and pathology ≤ LSIL were P16 negative. Results The accuracy rate of LBC for detection of pathology ≥ HSIL was 86.9% (93/107) in age group of ≥ 50, significantly lower than that of 95.5% (105/110) in age group of < 50 years (P = 0.026). P16 immunocytochemical stains on cases with cytology ≥ HISL and pathology ≤ LSIL were all negative in both groups. Conclusion The misinterpretation of LBC- ≥HSIL was rated higher in older women. P16 immunocytochemical stain works well in differentiating atrophic changes from LBC- ≥HSIL.

show abstract

Section: Discussionmentioning

confidence: 98%

Performance of P16 INK4a immunocytochemical stain in facilitating cytology interpretation of HSIL for women aged 50 and above

Hou,

Du,

Wang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Not much is known about the clinical use of dual p16/Ki67 staining in populations of women over 50 years of age. A recent study showed that double-stained cytology shows high sensitivity and specificity profiles for CIN2+ in postmenopausal women [44,45]. Previous studies have suggested a protective role of the HPV vaccine in women who already had an HPV infection, although the exact mechanism of this phenomenon and its clinical impact have not been fully clarified [46,47].…”

Section: Discussionmentioning

confidence: 99%

“…Exocervical cytologic samples were taken and placed in ThinPrep solution. Samples were sent to the laboratory for DNA extraction and viral DNA genotyping by genetic amplification followed by hybridization with genotype-specific probes capable of identifying most HPV genotypes of the genital region; high-risk HPV genotypes (16,18,26,31,33,35,39,45,51,52,53,56,58,59, 66, 68, 73, and 82), low risk (6, 11, 40, 43, 44, 54, and 70) and indefinite risk (69, 71, and 74). The commercial method used was the MAG NucliSenseasy system (bioMerieux SA, Marct l'Etoile, France).…”

Section: Hpv Dna Testing and Hpv Genotypingmentioning

confidence: 99%

“…Human papillomavirus (HPV) infection is a sexually transmitted disease due to the persistence of high-risk HPV genotypes whose prevalence shows significant differences worldwide [2,3]. In the most recent evaluation by the International Agency for Research on Cancer (IARC), 12 genotypes (HPV16, 18,31,33,35,39,45, 51, 52, 56, 58, and 59) were classified as carcinogenic, and HPV 68 and 66 have been classified as probably carcinogenic to humans (group 2A). Therefore, several HPV types have been characterized as oncogenic, but not all have the same carcinogenic potential; HPV16, in particular, has shown unique carcinogenic potential.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Extended Genotyping to Stratify the Risk of CIN2+ in Women with Persistent HPV Infection, Negative Cytology and Type 3 Transformation Zone

Bruno,

Valenti,

Cavallaro

et al. 2024

Cancers

Self Cite

View full text Add to dashboard Cite

Persistent human papillomavirus (HPV) infection is recognized as a major risk factor for cervical cancer. Women with persistent HPV and negative cytology are at greater risk of CIN2+ than women with negative infection. The diagnosis becomes more complicated when the woman has a type 3 transformation zone at colposcopy. The aim of this study was to determine the prevalence of CIN2+ in women with persistent HPV, negative cytology and TZ3; how to stratify the risk of CIN2+; and what the best diagnostic strategy is, given TZ3. Methods: In a multicenter retrospective cohort study, we enrolled women with negative cytology and TZ3 among the 213 women referred for colposcopy for persistent HPV. The average age of the women was 53 years; in particular, 83% were postmenopausal women. In the presence of a TZ3, the entire transformation zone cannot be explored, making colposcopy and targeted biopsy useless and inadequate, with great risks of underdiagnosis or missed diagnosis. Women with TZ3 underwent diagnostic LEEP to ensure correct diagnoses. Results: The study highlighted 19% (16/84) of CIN2+ lesions, a higher frequency of non-HPV 16/18 genotypes (76.2%), and 50% of CIN2+ lesions being due to non-HPV 16/18 genotypes. Furthermore, more than half of the women (80.9%) had normal histopathological results in the LEEP sample. Conclusion. Women with viral persistence, negative cytology, and TZ3 have a 19% risk of CIN2+; genotyping helps stratify risk, but extensive genotyping is necessary instead of partial genotyping (16/18), referring to a population of women over 50 years old in which the prevalence of genotypes 16,18 decreases and the prevalence of other genotypes increases; diagnostic LEEP is excessive (only 16 cases of CIN2+ out of 48 cases treated), even though 83% of women had viral clearance after LEEP; p16/Ki67 double staining could be a potential risk marker, which would only highlight women at risk of CIN2+ to undergo LEEP. To individualize the diagnostic workup and treatment and minimize the risk of under diagnosis and overtreatment, future studies should explore the use of extended genotyping and new biomarkers for individual risk stratification.

show abstract

“…[2][3][4] Previous studies have shown that menopausal status also represents a risk factor for residual or occult disease. Cervical atrophy secondary to the lack of estrogen induces the ascent of the entire transformation zone (Type 3 Transformation Zone), making both cytology and colposcopy ineffective [5,6]. The cervixes of these women are often small and with an unexplorable cervical canal, so it can also be difficult to perform a LEEP, the cone of which should be longer (15-20mm) than in young women (7-10mm).…”

Section: Introductionmentioning

confidence: 99%

VaIN after Hysterectomy is Strongly Associated with Persistent HR-HPV Infection

Bruno,

Panella,

Valenti

et al. 2024

Preprint

View full text Add to dashboard Cite

Previous studies show that women with a history of high-grade CIN have a greater risk of subsequent high-grade anogenital intraepithelial neoplasia or cancer, and the risk is greater for vaginal cancer than for anal and vulvar cancers. It is hypothesized that the laparoscopic hysterectomy procedure may cause a higher incidence of VaIN in hysterectomized women. There are few studies addressing this issue and they show mixed results. This study aimed to investigate the incidence of high-grade or worse VaIN in the population of women undergoing hysterectomy for CIN3 or benign uterine disease, illustrate treatment options and follow-up. Methods: This retrospective study was conducted on 170 women who underwent laparoscopic hysterectomy for high-grade cervical intraepithelial neoplasia (CIN3) or benign gynecological disease. The follow-up strategy included performing a cotest and colposcopy with biopsy if necessary. The median time between primary treatment and diagnosis of high-grade VaIN was 18 months. Results: High grade or worse VaIN was found in 8 patients after hysterectomy (4.7%). All cases of high-grade VaIN occurred in women with persistent HPV infection. The most frequent genotype was 16. Women hysterectomized for CIN3 showed an 8-fold greater risk than women hysterectomized for benign disease of developing high-grade VaIN. The risk of VaIN is low in women hysterectomized for benign disease. The risk of developing VaIN is greater in women with viral persistence Conclusion. All these elements suggest that it is the history of HPV-related disease of the lower genital tract and viral persistence, rather than hysterectomy itself, that should be considered a risk factor for the development of high-grade VaIN. After hysterectomy, patients with a history of CIN should undergo annual screening with vaginal dome cytology and HPV testing.

show abstract

Performance of p16/Ki67 Immunostaining for Triage of Elderly Women with Atypical Squamous Cells of Undetermined Significance

Cited by 4 publications

References 31 publications

Performance of P16 INK4a immunocytochemical stain in facilitating cytology interpretation of HSIL for women aged 50 and above

Performance of P16 INK4a immunocytochemical stain in facilitating cytology interpretation of HSIL for women aged 50 and above

Extended Genotyping to Stratify the Risk of CIN2+ in Women with Persistent HPV Infection, Negative Cytology and Type 3 Transformation Zone

VaIN after Hysterectomy is Strongly Associated with Persistent HR-HPV Infection

Contact Info

Product

Resources

About