The presence of persistent high‐risk hpv genotypes in dysplastic cervical lesions is associated with progressive disease: Natural history up to 36 months

Abstract

To evaluate the clinical significance of HPV genotyping for the prediction of progressive cervical intraepithelial neoplasia (CIN) in women with cytomorphologically abnormal smears, a prospective, blind, non-intervention study was performed. A total of 342 patients screened with cytomorphologically abnormal cervical smears were monitored every 3-4 months by cervical cytology, colposcopy and HPV testing using PCR. Women with progressive CIN disease were defined as patients developing lesions with a colposcopic impression of CIN III over more than 2 quadrants or resulting in a cytological smear equivalent to Pap 5. These patients were subsequently treated according to standard procedures. If any doubt arose about the true status of the patients (n = 75) these patients were censored and biopsied. The mean follow-up time was 16.5 months (range 3-36 months). Nineteen women showed progressive CIN disease and all appeared to be continuously HPV-positive from the start of the study. At biopsy, all these patients were histologically classified as CIN III. Seventeen of these women were positive for high-risk HPV types. Two cases were classified as still unidentified HPV. No progression was seen in the absence of HPV DNA or in the presence of low-risk HPV types. In life-table analysis the cumulative rate of progressive, histologically verified CIN disease was 17% after 36 months. Further analyses showed that other risk factors such as age, sexarche, number of sexual partners or smoking hardly influenced the effect of HPV on progression. The results show that the continuous presence of high-risk HPV types in women with cytomorphologically abnormal smears is a strong marker for progressive CIN disease.

High-risk human papillomavirus clearance in pregnant women: trends for lower clearance during pregnancy with a catch-up postpartum

“…Women were monitored every 3 to 4 months by cytology, colposcopy and HPV testing (Remmink et al, 1995;Nobbenhuis et al, 1999Nobbenhuis et al, , 2001. Clinicians and laboratory staff were blinded for HPV test results and clinical findings, respectively.…”

“…Keywords: human papillomavirus; pregnancy; follow-up study; natural history; prevalence Several epidemiological and biological studies have established the important role of infection with high-risk types of human papilloma virus (HPV) for development of cervical cancer and its precursor lesions. In women with or without abnormal cervical smears a positive high-risk HPV test result indicates an increased risk for development of high grade cervical lesions (Ho et al, 1995;Remmink et al, 1995;Rozendaal et al, 1996Rozendaal et al, , 2000Nobbenhuis et al, 1999). Moreover, in nearly all cervical cancers high-risk HPV types have been detected .…”

A systematic review of the role of human papilloma virus (HPV) testing within a cervical screening programme: summary and conclusions

“…Most infections are transient, with a median duration of at most 12 months, and pose no risk of cervical neoplasia: only the 10-20% that remain persistent are of concern (Ho et al, 1995;Remmink et al, 1995;Nobbenhuis et al, 1999). Evidence of infection, either by serology in stored blood samples or by viral DNA in fixed archival specimens, is found many years before serious disease is present, and indicates that infection precedes disease (Walboomers et al, 1995;Lehtinen et al, 1996;Dillner et al, 1997). Detection of HPV DNA in the absence of cytological abnormalities can also indicate presence of high-grade cervical intraepithelial neoplasia (CIN) which was missed by cytology .…”

Triage using HPV‐testing in persistent borderline and mildly dyskaryotic smears: Proposal for new guidelines

“…25 This test has been clinically validated. 11,26,27 Additionally, reverse line blot (RLB) analysis was used to identify individual HPV types in case the PCR-EIA was positive. 25 We used b-globin PCR to identify sampling errors and to monitor for PCR inhibitors.…”

“…7,8 Persistence of hrHPV infection is required for development of cervical cancer. [9][10][11][12] Several studies have shown that HPV testing has a high sensitivity (approximately 95%) for identifying high-grade lesions and cervical carcinoma. Moreover, the negative predictive value of HPV testing for detection of a high-grade CIN lesion or even (micro)invasive carcinoma is nearly 100%.…”