Article

Human Papillomavirus testing and liquid-based cytology in primary cervical screening: results at recruitment from the NTCC randomized controlled trial

Unit of Cancer Epidemiology, Centro per la Prevenzione Oncologica Piemonte, 10123 Turin, Italy.
CancerSpectrum Knowledge Environment (Impact Factor: 15.16). 06/2006; 98(11):765-74. DOI: 10.1093/jnci/djj209
Source: PubMed

ABSTRACT Although testing for human papillomavirus (HPV) has higher sensitivity and lower specificity than cytology alone for detecting cervical intraepithelial neoplasia (CIN), studies comparing conventional and liquid-based cytology have had conflicting results.
In the first phase of a two-phase multicenter randomized controlled trial, women aged 35-60 years in the conventional arm (n = 16,658) were screened using conventional cytology, and women in the experimental arm (n = 16,706) had liquid-based cytology and were tested for high-risk HPV types using the Hybrid Capture 2 assay. Women in the conventional arm were referred to colposcopy with atypical cells of undetermined significance (ASCUS) or higher and those in the experimental arm were referred with ASCUS or higher cytology or with a positive (> or = 1 pg/mL) HPV test. Sensitivity and positive predictive value (PPV) for detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) were calculated.
The screening methods and referral criterion applied in the experimental arm had higher sensitivity than that in the conventional arm (relative sensitivity = 1.47; 95% confidence interval [CI] = 1.03 to 2.09) but a lower PPV (relative PPV = 0.40; 95% CI = 0.23 to 0.66). With HPV testing alone at > or = 1 pg/mL and at > or = 2 pg/mL, the gain in sensitivity compared with the conventional arm remained similar (relative sensitivity = 1.43, 95% CI = 1.00 to 2.04 and relative sensitivity = 1.41, 95% CI = 0.98 to 2.01, respectively) but PPV progressively improved (relative PPV = 0.58, 95% CI = 0.33 to 0.98 and relative PPV = 0.75, 95% CI = 0.45 and 1.27, respectively). Referral based on liquid-based cytology alone did not increase sensitivity compared with conventional cytology (relative sensitivity = 1.06; 95% CI = 0.72 to 1.55) but reduced PPV (relative PPV = 0.57; 95% CI = 0.39 to 0.82).
HPV testing alone was more sensitive than conventional cytology among women 35-60 years old. Adding liquid-based cytology improved sensitivity only marginally but increased false-positives. HPV testing using Hybrid Capture 2 with a 2 pg/mL cutoff may be more appropriate than a 1 pg/mL cutoff for primary cervical cancer screening.

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    • "Methods of recruitment and randomisation of NTCC study have been previously described [24-26]. Briefly, following an invitation sent to the entire target population, women aged 25–60 years attending a new round of cervical screening were assigned randomly to either conventional cytology or HPV testing arm. "
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    ABSTRACT: Background Although among women a decreasing prevalence of human papillomavirus (HPV) infection with increasing age has been consistently observed in high-resource countries, different age profiles have been reported elsewhere. Methods We compared the age profile of high-risk (HR)-HPV prevalence in nine different areas of Northern and Central Italy by studying the women recruited in the intervention arm of the New Technologies in Cervical Cancer study and tested by Hybrid Capture 2. Differences in the age-distribution of HPV infection were investigated in each centre by the joinpoint approach in a logistic model. 46,900 women aged 25 to 60 years were included in the analysis. Results The HR-HPV age-standardised (on Italian population) prevalence ranged from 5.7% (Trento) to 10.3% (Ravenna). HR-HPV prevalence decreased as a logistic function of increasing age in 6 of 9 centres (Trento, Verona, Florence, Bologna, Imola, and Viterbo). The effect of age on HR-HPV prevalence slopes did not differ significantly among these 6 centres, whereas significant heterogeneity in intercepts (p < 0.001) was found, reflecting different overall HR-HPV prevalence between centres. One significant joinpoint was observed in 2 centres (Padua and Ravenna), indicating that the decrease in HR-HPV prevalence by age was better described using a function composed with two logistic segments. In Padua HR-HPV prevalence decreased only slightly up to 39 years but showed a steep downturn thereafter. In Ravenna HR-HPV prevalence decreased steeply down to 45 years of age and then showed a plateau. Finally, in Turin two significant joinpoints were observed: prevalence decreased only after age 29 and showed a plateau after age 39. Conclusions Our results showed substantial differences in overall and age-specific HR-HPV prevalence across Italian areas. These findings may be related to different timing of changes in sexual behaviours across regions. Age-specific HR-HPV prevalence in Italy does not support an influence of age per se.
    BMC Infectious Diseases 05/2013; 13(1):238. DOI:10.1186/1471-2334-13-238 · 2.61 Impact Factor
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    • "Most newly acquired HPV infections regress spontaneously, and HPV DNA positivity decreases with age following a peak in adolescents and in women in their 20s [24]. Therefore, the HPV DNA test in combination with a cervical cytology test is recommended for women ≥30 years old (HS) [25-43]. When both tests are negative, the screening interval can be extended to 2 years (HS). "
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    ABSTRACT: The consensus guideline development committee of Korean Society of Gynecologic Oncology was reconvened in March 2012. The committee consisted of 36 experts representing 12 university hospitals and professional organizations. The objective of this committee was to develop standardized guidelines for cervical cancer screening tests for Korean women and to distribute these guidelines to every clinician, eventually improving the quality of medical care. Since the establishment of the consensus guideline development committee, evidence-based guidelines have either been developed de novo considering specific Korean situations or by adaptation of preexisting consensus guidelines from other countries. Recommendations for cervical cancer screening tests, management of atypical squamous and glandular cells, and management of low-grade and high-grade squamous intraepithelial lesions were developed. Additionally, recommendations for human papillomavirus DNA testing and recommendations for adolescent and pregnant women with abnormal cervical screening test results were also included.
    Journal of Gynecologic Oncology 04/2013; 24(2):186-203. DOI:10.3802/jgo.2013.24.2.186 · 1.60 Impact Factor
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    • "As expected, we found that women with cervical cytological abnormalities were at significantly increased risk for being infected by HR-HPV types than women with normal cytology (52 vs. 15%). Current Italian studies involving women with cytological abnormalities (different ages and enrolment criteria) reported HR-HPV prevalence of 34-68%, increasing with cytology severity: 24-56% in case of diagnosis of ASCUS/AGUS, 42-72% in LSIL and 73-95% in HSIL [21,22,26,27,30-32]. "
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    ABSTRACT: Background Pre-vaccination information on HPV type-specific prevalence in target populations is essential for designing and monitoring immunization strategies for cervical cancer (CC) prevention. Data on HPV prevalence in Italy are available for women over the age of 24 years, target of the population-based CC screening programmes; while data of HPV prevalence in younger ages are very limited. The present study enrolled Italian women aged 18–26 years in order to assess the prevalence and distribution of high-risk (HR) HPV types. Risk-factors correlated with HR-HPV positivity were also described. Methods A sample of 2,289 women was randomly selected from the resident population lists of ten Local Health Units (LHUs) located in six Italian Regions scattered across the country; both rural and urban LHUs were involved. Women aged between 18 and 26 years and living in the selected LHUs were included in the study; pregnant women and women who did not speak Italian were excluded. A total of 1,102 women met the inclusion criteria and agreed to participate. Participants were offered pap test and Hybrid-Capture 2 (HC2) test for HR-HPV types and genotyping was performed on positive smears. Results Out of 1,094 valid samples, 205 (18.7%) were HR-HPV positive. Women with 2–4 (ORadj = 4.15, 95%CI: 2.56-6.72) and ≥5 lifetime partners (ORadj = 10.63, 95%CI: 6.16-18.36) and women who have used any contraceptive in the last six months (ORadj = 1.67, 95%CI: 1.09-2.54) had a higher risk to be infected; women living with their partner had a lower risk (ORadj = 0.56, 95%CI: 0.34-0.92) to acquire infection than women living with parents/friends/alone. Among HC2 positive women, HPV16 was the most prevalent type (30.9%), followed by 31 (19.6%), 66 (12.9%), 51 (11.3%), 18 (8.8%), 56 (8.8%). Co-infections of HR-HC2 targeted types were found in 20.4% of positive samples. The HR-HPV prevalence in women with abnormal cytology (52.4%) was significantly higher than in women with normal cytology (14.6%); however 33.0% of HR-HPV infected women had an abnormal cytology. Conclusion HR-HPV prevalence in Italian women aged 18–26 years was 19%, higher than what detected for older women, by other studies using the same molecular method and laboratory network; this result supports the choice of electing girls before the sexual debut as the primary target of HPV vaccination. The HPV type distribution found in this study may represent a baseline picture; an accurate post-vaccine surveillance is necessary to early detect a possible genotype replacement. The high prevalence of viral types other than vaccine-HPV types supports the necessity to guarantee the progression of CC screening programmes in vaccinated women.
    BMC Infectious Diseases 02/2013; 13(1):74. DOI:10.1186/1471-2334-13-74 · 2.61 Impact Factor
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