Morphometric evaluation and nonclassical criteria for the diagnosis of HPV infection and cytological atypia in cervical samples

Abstract

Herein, we evaluated cervical samples from normal tissue or HPV-infected tissue, to determine if the relative nuclear/cytoplasmic ratio (NA/CA) and the presence of nonclassical cytological criteria are a novel cytological criterion for the diagnosis of HPV. Significantly, larger NA/CA ratios were found for the HPV-ATYPIA+ and HPV+ATYPIA+ groups compared with HPV-ATYPIA- group, regardless of collection method. For the samples collected with a spatula, only three samples from the HPV-ATIPIA- group showed four or more nonclassical parameters (i.e., were positive), while a larger number of the samples in the HPV-ATYPIA+, HPV+ATYPIA-, and HPV+ATYPIA+ groups were positive (13, 4, and 13 samples, respectively). Among those collected with a brush, no sample showed four or more nonclassical criteria in the HPV-ATYPIA- group, while a number of samples were positive in the HPV-ATYPIA+, HPV+ATYPIA-, and HPV+ATYPIA+ groups (4, 3, and 4 samples, respectively). HPV infection was associated with significant morphometrical changes; no increase in the NA/CA ratio was found in the HPV+ATYPIA- samples, compared with the HPV-ATIPIA- samples collected with either a spatula or a brush. In conclusion, by including nonclassical cytological criteria into the patient diagnosis, we were able to reduce the number of false negative and false positive HPV diagnoses made using conventional cytology alone.

Investigation of the Possible Cytopathological Effect of Human Papillomavirus Infection on p-16INK4a Overexpressed Urothelial Carcinomas of the Bladder in the Urine

“…These cells appear mainly at the stages of CIN1 and CIN2 but are rare in the stage of invasive cancer, except when associated with CIN1 and CIN2 lesions. HPV infection is not only involved in squamous cell carcinoma, but also adenocarcinoma in the uterine cervix [30,31]. However, the cellular changes of HPV infection in glandular cells are not well established.…”

“…Atypical squamous cells that appeared in urine cytology specimens of HPV-DNA positive cases in this study were of the "Non-classic type" rather than "Classic type" which includes koilocytes and dyskeratotic cells. There are many established reports of the appearance of atypical squamous cells of nonclassic type in uterine cervical smears, and there are types of observed parameters or combination of parameters indicative of HPV infection [20,31]. However, atypical squamous cells that appeared in HPV-DNA positive cases were observed in both cases of the voided urine and it was not possible to limit them from the urinary bladder epithelium.…”

Modernas metodologías diagnosticas para la detección del Virus del Papiloma Humano y prevención del cáncer de cuello uterino

“…Posteriormente, la proteína L1 realiza un cambio de forma que le permite su unión a un receptor que se considera es el complejo integrina α6β4 en la membrana del queratinocito permitiendo su entrada por medio de mecanismos como endocitosis mediada por clatrina, endocitosis caveolar, endocitosis independiente de clatrina o caveolas 4,5 . Posteriormente el virión infectará a los queratinocitos epiteliales basales, llevando a cabo su proceso de replicación y transformando los queratinocitos en coilocitos (células infectadas), iniciando el proceso de tumorgénesis como se describe en la Figura 2, proceso que puede ser detectado por métodos directos como la citología cervical 2,5,6 .…”

“…Es una técnica que utiliza una fase liquida que permite la hibridación por complementariedad del ADN viral con el ARN sintético de 13 genotipos de VPH-AR (16,18,31,33,35,39,45, 51, 52, 56, 58, 59 y 68) y cinco VPH-BR (6,11,42, 43 y 44). La hibridación es captada por anticuerpos fijados en los pozos de la microplaca, se elimina el exceso de reactivos, se agrega un revelador luminiscente y la emisión de luz es proporcional a la cantidad de ADN, otorgando una medida semicuantitativa de la carga viral 25 .…”

Cytomorphometry and morphology analysis of human papillomavirus type 16 in liquid‐based cervical cytology samples

“…In exfoliative cytology, nuclear and cellular size, morphology and the nuclear‐to‐cytoplasmic ratio are the most useful parameters 24 . Some morphometric and morphological criteria have been proposed to increase the sensitivity of conventional Pap smear and thin prep cytology 25,26 . Nonclassical criteria for HPV diagnosis have been proposed to increase the sensitivity of standard methods 25 …”