The probability for a Pap test to be abnormal is directly proportional to HPV viral load: results from a Swiss study comparing HPV testing and liquid-based cytology to detect cervical cancer precursors in 13 842 women

Abstract

In a study involving 13 842 women and 113 gynaecologists, liquid-based cytology and HPV testing for detecting cervical cancer were compared. A total of 1334 women were found to be positive for one or both tests and were invited for colposcopy with biopsy. A total of 1031 satisfactory biopsies on 1031 women were thereafter collected using a systematic biopsy protocol, which was random in the colposcopically normal-appearing cervix or directed in the abnormal one. In all, 502 women with negative tests were also biopsied. A total of 82 histologic high-grade squamous intraepithelial lesion (HSIL) were reported in biopsies, all from the group with one or both tests positive. Sensitivity and specificity to detect histologic HSIL were 59 and 97% for cytology, and 97 and 92% for HPV. In total, 14% of reviewed negative cytological preparations associated with histologic HSIL contained no morphologically abnormal cells despite a positive HPV test. This suggested a theoretical limit for cytology sensitivity. HPV viral load analysis of the 1143 HPVpositive samples showed a direct relationship between abnormal Pap test frequency and HPV viral load. Thus, not only does the HPV testing have a greater sensitivity than cytology but the probability of the latter being positive can also be defined as a function of the associated HPV viral load.

Cost effectiveness of high-risk HPV DNA testing for cervical cancer screening in South Africa

“…Cytology test results were classified according to the 2001 Bethesda system [38]. HPV testing was used to identify the 13 known high-risk HPV types (16,18,31,33,35,39,45,51,52,56,58,59, and 68). Women with abnormal screening results were referred for follow-up colposcopies or repeat screening, and the presence of a cervical lesion was confirmed using colposcopy and biopsy [29][30][31]39,40].…”

High load for most high risk human papillomavirus genotypes is associated with prevalent cervical cancer precursors but only HPV16 load predicts the development of incident disease

“…Although HPV testing is clinically useful, many women with self-limited carcinogenic HPV infections test positive and are subjected to unnecessary procedures. Therefore, identifying markers that indicate which HPV infections will persist and result in progression to cancer precursors is an important research objective.High concentration of HPV DNA in cervical specimens (HPV viral load) [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] has been evaluated as a marker for the presence of prevalent cervical cancer precursors (defined in the United States for treatment purposes as CIN2 or worse, CIN2) or incident CIN2. Following a typical infectious disease model, viral load as a measure of ''dosage'' (i.e., HPV copy number) might be predictive of CIN2 or the duration of infection.…”

Associação entre a carga viral de HPV de alto risco, expressão de p16INK4a e lesões intra-epiteliais escamosas do colo uterino

“…Deve ser tomado cuidado com a possibilidade de quadros de latência levarem a falsos positivos e, portanto, sobrediagnóstico. A possibilidade de diferença entre a carga viral e o diagnóstico da lesão tem sido estabelecida em vários estudos 6,7,8,10,12,13,15,18,22 , embora contestados por outros 23,24 . De fato, o "cutoff" que permite uma melhor performance do teste no diagnóstico de HSIL tem sido bastante variável.…”

“…Assim, hoje se sabe que o tipo 16 é o mais prevalente em todo o mundo 1 , independentemente da gravidade da lesão escamosa, e, de maneira geral, os HPV identificados como de alto risco estão presentes em mulheres imunocompetentes em cerca de 20% dos quadros histológicos negativos, em 70% dosUNIOR UNIOR*, P *, P *, P *, P *, PAULO AULO AULO AULO AULO C C C C CÉSAR ÉSAR ÉSAR ÉSAR ÉSAR G G G G GIRALDO IRALDO Vários pesquisadores defendem a idéia de que a alta carga viral de HPV de alto risco teria uma importante relação com lesões intraepiteliais escamosas e sua maior gravidade 6,7,8,10,12,15,18,22 . Outros pesquisadores enfatizam a importância da persistência da alta carga viral por longo tempo, e não simplesmente uma medida isolada, assim como só teria valor a alta carga viral do HPV tipo 16, sem considerar os demais tipos 2,3,9,13,14,16,17 .…”

“…Assim, a persistência de vírus de alto risco 5 , alta carga viral 2, 6-15 , persistente alta carga viral 16,17,18 , expressão do marcador de proliferação MIB-1 19 e, finalmente, a expressão do marcador de supressão tumoral p16 INK4a 4,20,21 , estão sendo apontados como prováveis marcadores de diagnóstico de lesões escamosas de alto grau e de seu prognóstico. Vários pesquisadores defendem a idéia de que a alta carga viral de HPV de alto risco teria uma importante relação com lesões intraepiteliais escamosas e sua maior gravidade 6,7,8,10,12,15,18,22 . Outros pesquisadores enfatizam a importância da persistência da alta carga viral por longo tempo, e não simplesmente uma medida isolada, assim como só teria valor a alta carga viral do HPV tipo 16, sem considerar os demais tipos 2,3,9,13,14,16,17 .…”