Human papillomavirus (HPV)-associated trilateral squamous neoplasia in immunocompetent individual.

PURPOSE: To describe a case of bilateral conjunctival and cervical human papillomavirus (HPV)-related squamous neoplasia. CASE DESCRIPTION: A healthy immunocompetent 55-year-old lady came to our attention for prosecution of care of a right recurrent conjunctival squamous cell carcinoma. Upon examination, she was found disease-free in the right eye but displayed a left conjunctival intraepithelial neoplasia (CIN grade I) and low-grade cervical squamous dysplasia. HPV infection with genotypes 16 (right eye), 11 and 39 (left eye) and 39 (uterine cervix) was also detected. CONCLUSION: Simultaneous uterine and conjunctival HPV-related squamous neoplasia can occur in immunocompetent individuals. Auto-inoculation and repeated exposure to HPV could explain coexistence of different genotypes.

Age-related changes in pre- and post-conization HPV genotype distribution among women with high-grade cervical intraepithelial neoplasia.

OBJECTIVE: To assess the effect of age on pre- and post-conization HPV genotype distribution. METHODS: The present retrospective observational study included consecutive women with high-grade cervical intraepithelial neoplasia who underwent conization at the Cervical Cancer Screening Centre of Reggio Emilia, Italy, and University Hospital of Modena, Italy, between February 1, 2012, and October 31, 2014. Pre-conization and 6-month post-conization HPV genotyping results were compared between four age groups (<30, 30-39, 40-49, and ≥50 years) and age-related changes in the HPV genotypes present were evaluated. RESULTS: There were 162 patients included. The lowest occurrence of pre-conization high-risk and probable high-risk HPV genotypes was observed among patients aged at least 50 years when compared with younger patients (P=0.017). Conversely, women aged at least 50 years exhibited the highest level of post-conization high-risk and probable high-risk HPV genotypes (P=0.043). Additionally, an increasing incidence of recording identical pre- and post-conization HPV genotypes was associated with increasing age (P=0.024), as was increasing post-treatment recurrence of cervical intraepithelial neoplasia grade 2+ (P=0.030). CONCLUSION: The presence of high-risk and probable high-risk HPV genotypes was lowest among older patients before conization and was highest among these patients post-conization; post-treatment HPV clearance decreased with age and increasing age could be a risk factor for post-conization recurrence.

Interobserver reproducibility of cytologic p16INK4a /Ki-67 dual immunostaining in human papillomavirus-positive women.

BACKGROUND: The accumulation of cyclin-dependent kinase inhibitor 2A (p16ink4a ) protein in a cell is associated with neoplastic progression in precancerous cervical lesions. Dual staining for p16ink4a and Ki-67 has been proposed as a triage test in cervical cancer screening for women who test positive for human papillomavirus DNA. In this study, interobserver reproducibility of the interpretation of this test was assessed. METHODS: Forty-two immunostained, liquid-based cytology slides were divided into 2 sets and were interpreted by 17 to 21 readers from 9 different laboratories, yielding a total of 816 reports. Immunostaining results were classified as positive, negative, inconclusive, or inadequate. After evaluation of the first set of slides and before circulation of the second set, the results were discussed in a plenary meeting. The 10 slides with the most discordant results were evaluated again by selected expert cytopathologists. RESULTS: The overall κ value was 0.612 (95% confidence interval [CI], 0.523-0.701), it was higher for the positive and negative categories (κ = 0.692 and κ = 0.641, respectively), and it was almost null for the inconclusive category (κ = 0.058). Considering only readers from laboratories with documented experience, the κ value was higher (κ = 0.747; 95% CI, 0.643-0.839) compared with nonexperienced centers (κ = 0.498; 95% CI, 0.388-0.616). The results were similar in both sets of slides (κ = 0.505 [95% CI, 0.358-0.642] and κ = 0.521 [95% CI, 0.240-0.698] for the first and second sets, respectively). Reinterpretation of the slides with the most discordant results did not provide any improvement (first evaluation, κ = 0.616 [95% CI, 0.384-0.866]; second evaluation, κ = 0.403 [95% CI, 0.182-0.643]). CONCLUSIONS: Dual staining for p16 ink4a and Ki-67 demonstrated good reproducibility, confirming its robustness, which is a necessary prerequisite for its adoption as a triage test in cervical cancer screening programs that use human papillomavirus DNA as a primary test. Cancer Cytopathol 2017;125:212-220. © 2016 American Cancer Society.

Outcome of Nonpersonalized Human Papillomavirus Vaccinations During Postconization Follow-up: A Report of Two Cases.

BACKGROUND: The human papillomavirus (HPV) vaccine was conceived to prevent new HPV infections among uninfected young women. From the initial intentions, its use has been extended to older women and also tested as a therapeutic tool. We report two HPV vaccination outcomes during postconization follow-up. CASES: Two young women, with different clinical histories, were subjected to HPV vaccine after a loop electrosurgical excision procedure for high-grade cervical intraepithelial neoplasia (CIN) and persisting low-grade CIN. During follow-up both women experienced a worsening of cervical lesions, which resulted in invasive cervical cancer and severe dysplasia, respectively. CONCLUSION: Limited to our experience, a nonpersonalized HPV vaccine administration during postconization follow-up was expensive and unnecessary.

High-grade CIN on cervical biopsy and predictors of the subsequent cone histology results in women undergoing immediate conization.

OBJECTIVE: To identify the clinical/colposcopic variables that associate with low-grade/negative cone histology in screening-age women undergoing conization for high-grade cervical intraepithelial neoplasia (CIN). The follow-up outcomes of study participants were also compared. STUDY DESIGN: In this retrospective cohort study, 585 consecutive screening-age women who underwent immediate conization for CIN2-3 were divided according to cone histology (CIN2+ versus ≤CIN1) and assessed in relation to clinical/colposcopic variables by univariate and multivariate analyses. RESULTS: Low-grade [adjusted odds ratio (AOR)=52.67, 95% confidence interval (CI) 22.49-123.34] or normal (AOR=9.81, 95% CI 2.38-40.44) colposcopic impression and CIN2 on cervical biopsy (AOR=19.59, 95% CI 6.62-57.92) associated with CIN1/negative cone histology. Multivariate analysis also showed that Eastern European ethnicity (AOR=0.13, 95% CI 0.03-0.52) and high-risk-Human Papillomavirus (hr-HPV)-positivity (AOR=0.38, 95% CI 0.17-0.87), associated with CIN2+ cone histology. Overall, there were no significant differences between the two groups in terms of high-grade recurrence during the 2-year follow-up. Conversely, a higher rate of high-grade recurrence was present in CIN2-3 (positive cone margins) than in CIN1/negative cone histology (21.9% versus 7.4%, P=0.008, respectively). CONCLUSION: The presence of CIN2 on cervical biopsy and a low-grade colposcopic impression were predictive of a minor cone histology, unless the subject was of East European ethnicity or was positive for hr-HPV test. Given the follow-up outcomes, the same women need to perform a close monitoring. However, positive cone margins in women with CIN2-3 cone histology seem to define a population at greater risk of high-grade recurrence.