Difference in overall and age-specific prevalence of high-risk human papillomavirus infection in Italy: evidence from NTCC trial

Baussano, Iacopo; Franceschi, Silvia; Gillio-Tos, Anna; Carozzi, Francesca; Confortini, Massimo; Palma, Paolo Dalla; Lillo, Margherita De; Mistro, Annarosa Del; Marco, Laura De; Naldoni, Carlo; Pierotti, Paola; Schincaglia, Patrizia; Segnan, Nereo; Zorzi, Manuel; Rossi, Paolo Giorgi; Ronco, Guglielmo

doi:10.1186/1471-2334-13-238

Cited by 18 publications

(18 citation statements)

References 36 publications

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“…Infections positive for HPV decreased as age of the participants increased. This data coincides with findings obtained in work recently carried out in Italy, in which the prevalence of HR HPV genotypes had a significant increase in women younger than 35 years of age to later decrease as age of the participants increased [ 52 ]. The decrease in prevalence of HPV infection as age increases is frequently defined by changes in sexual behaviour and elimination of the infectious process mediated by the localised action of the elements of the immunological system of the affected person [ 53 ].…”

Section: Discussionsupporting

confidence: 91%

Persistent infection with high-risk human papilloma viruses: cohort study, Mérida, Venezuela

Téllez

Michelli²,

Mendoza

et al. 2015

ecancer

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Cervical lesions have been associated with infection by high-risk human papilloma virus (high-risk HPV). In 409 women aged >15 years high-risk HPV lesions were identified. In a cohort of this population persistent infection was compared with cytological, colposcopic, and histological lesions. Cervical scrapes were taken and DNA was isolated. HPV was detected by PCR in the E6/E7 region. Genotyping was performed by PCR nested multiple E6/E7. HPV was detected in a 37.40% (153/409), high-risk HPV in 86% (153/178), HPV18 46.64% (83/178), HPV16 34.28% (61/178). Among these 53.93% (96/178) were multiple infections, and HPV18/16 (30/96) was the most frequent 31.25%. The cytology showed changes in 15% of positive patients. A 49.67% in women positive for HPV infection showed abnormalities in the colposcopic study, a relationship that turned out to be statistically significant ( p < 0.0019 test χ2). Among all 85% of the women were younger than 45 years of age. Fifty-seven patients were evaluated 15 months after the base study, with initial prevalence of morbidity 49.12% (28/57) and at the end 10.53% (6/57), showing in 89.29% (25/28) negative for HR-HPV infection, 10.34% (3/28) showed persistence of infection, 17.54% (10/57) presented cytological alterations, with 80% of positivity for HPV, and a regression of 100% (10/10) of the previously identified lesions. With colposcopy, 50% (14/28) presented alterations related to HPV, of these 85.71% (12/14) showed regression of such an alteration. The cumulative incidence for HPV was 10.34% (3/29). The incidence rate was 4.23% (3/71), which is equal to 4.23 new cases of HPV infection per 100 people, per year of follow-up. In conclusion, the present work shows a high frequency of infection by high-risk HPV, with predominance of HPV18 and 16 and in general for multiple infections. Colposcopy was better predictor than the Pap smear for infection. The follow-up study revealed a low percentage of persistent infection, and a high frequency of negativity for viral infection, high regression of cytological and colposcopic lesions, a low cumulative and incidence rate similar to that reported by other Latin American countries and higher than the European countries.

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Section: Discussionsupporting

confidence: 91%

Persistent infection with high-risk human papilloma viruses: cohort study, Mérida, Venezuela

Téllez

Michelli²,

Mendoza

et al. 2015

ecancer

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“…De SanJose reported the worldwide HPV prevalence via a meta‐analysis and found that the second peak of HPV prevalence in women after 44 years old presented with an area difference. For instance, in European and North American women, the HPV prevalence commonly declines after the age of 25 , while in Asian and Latin American women, the second rise in the HPV prevalence may emerge in some areas, such as China , Japan , Chile , Colombia , and Mexico . Some factors may be related to the second peak in the HPV prevalence, such as increased extramarital sexual behaviors of their husbands or themselves, or decreased immunity due to a female hormone decline during peri‐ or post‐menopause, which could lead to potential activation of HPV with a low replication status .…”

Section: Discussionmentioning

confidence: 99%

A cross‐sectional study on HPV testing with type 16/18 genotyping for cervical cancer screening in 11,064 Chinese women

Zhao

et al. 2017

Cancer Medicine

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Cytology‐based cervical cancer screening is restricted because of a lack of cytologists. Thus, HPV‐based instead of cytology‐based screening may be a more suitable strategy in China. Here, we assessed the effectiveness of HPV testing (Cobas® 4800 Test, Roche) and HPV‐based programs to detect high‐grade cervical intraepithelial neoplasia (CIN) or cancer compared with cytology (Thinprep, Hologic) and cytology‐based programs through a cross‐sectional study in 11,064 Chinese women aged 21–65 years who were enrolled from Longyou County in Zhejiang Province, China. The rates of HPV positivity and cytology abnormality were 9.8% and 6.1%, respectively. The HPV positivity rate had two age peaks, 21–24 (15.4%) and 60–65 (14.4%) years. According to adjusted data, HPV testing demonstrated significantly higher sensitivity and negative predictive value (NPV) than cytology for detecting CIN2 or worse (90.0% vs. 66.7%, 99.9% vs. 99.5%), and there was an acceptable specificity (91.3%) and positive predictive value (PPV, 12.5%). Furthermore, primary HPV testing with type 16/18 genotyping showed the highest sensitivity (78.6%) and NPV (99.7%) among four screening strategies, and there was similar specificity (96.8%) and PPV (23.9%) compared with co‐testing screening to detect CIN2+, while there were fewer colposcopies (4.2) and tests (106.3) performed than with co‐testing and primary cytology screening to detect a case of high‐grade CIN. The differences in effectiveness were approximately similar when CIN3+ was the identifying target. Our findings suggest that primary HPV testing with type 16/18 genotyping has a higher sensitivity and NPV, possesses optimal cost/effectiveness in the first round of screening and is a feasible strategy of cervical cancer screening for Chinese women.

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“…Welch's t -test or Wilcoxon rank Z test (42) were used for the descriptive statistical comparisons of the densitometric integrated intensity results concerning each protein's specific immunoblot bands from twice-negative controls vs. twice (LSIL/ASCUS and HPV DNA)-positive groups. For diagnostic statistics a prevalence of HPV infection of 0.31 was assumed by averaging observations from whole Italy (43, 44). The performance of diagnostic tests, i.e., their ability to correctly identify positive and negative cases over a range of medical decision points, was assessed using non-parametric empirical receiver-operating characteristic (ROC) curve analysis (45).…”

Section: Methodsmentioning

confidence: 99%

Over Expressed TKTL1, CIP-2A, and B-MYB Proteins in Uterine Cervix Epithelium Scrapings as Potential Risk Predictive Biomarkers in HR-HPV-Infected LSIL/ASCUS Patients

et al. 2019

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High oncogenic risk human papillomaviruses (HR-HPVs) promote cervical carcinoma development, the fourth most common feminine cancer. A slow oncodevelopmental phase—defined histopathologically as Cervical Intraepithelial Neoplasia (CIN) grades 1–3, or cytologically as Low- or High-grade Squamous Intraepithelial Lesions (LSIL or HSIL)—precedes the malignancy. Cervical carcinoma screenings through HR-HPV genotyping and Pap smears are regularly performed in Western countries. Faulty cytology screening or genotyping or patients' non-compliance with follow-ups can let slip an oncoprogression diagnosis. Novel biomarker tests flanking HR-HPV genotyping and cytology could objectively predict the risk of disease progression thus helping triage LSIL/ASCUS patients. Here, anonymized leftovers of fresh cervical epithelium scrapings from twice (LSIL/ASCUS and HR-HPV DNA)-positive and twice (Pap smear- and HR-HPV DNA)-negative (control) patients in a proteome-preserving solution served to assess the biomarker worth of three cervical carcinoma-related proteins, i.e., B-MYB (or MYBL2), Cancerous Inhibitor of PP2A (CIP-2a), and transketolase-like1 (TKTL1). Leftovers anonymity was strictly kept and storage at −80°C, protein extraction, immunoblotting, and band densitometry were blindly performed. Only after tests completion, the anonymous yet code-corresponding HR-HPV-genotyping and cytology data allowed to assign each sample to the twice-positive or twice-negative group. Descriptive statistics showed that the three proteins levels significantly increased in the twice-positive vs. twice-negative scrapings. Diagnostic ROC curve analysis identified each protein's Optimal Decision Threshold (OTD) showing that TKTL1 and CIP-2a are stronger risk predictive biomarkers (Sensitivity, 0.91–0.93; Specificity, 0.77–0.83) than B-MYB. Logistic Regression coupled with Likelihood-Ratio Tests confirmed that a highly significant relation links increasing TKTL1/CIP-2a/B-MYB protein levels in twice-positive cervical scrapings to the risk of HR-HPV-driven oncoprogression. Finally, a 3 year clinical follow-up showed that 13 patients (50% of total) of the twice-positive group with biomarker values over OTDs compliantly underwent scheduled colposcopy and biopsy. Of these, 11 (i.e., 84.7%) received a positive histological diagnosis, i.e., CIN1 ( n = 5; 38.5%) or CIN2/CIN2+ ( n = 6; 46,2%). Therefore, TKTL1/CIP-2a/B-MYB protein levels could objectively predict oncoprogression risk in twice (HR-HPV- and Pap smear)-positive women. Further studies will assess the translatability of these findings into clinical settings.

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Difference in overall and age-specific prevalence of high-risk human papillomavirus infection in Italy: evidence from NTCC trial

Cited by 18 publications

References 36 publications

Persistent infection with high-risk human papilloma viruses: cohort study, Mérida, Venezuela

Persistent infection with high-risk human papilloma viruses: cohort study, Mérida, Venezuela

A cross‐sectional study on HPV testing with type 16/18 genotyping for cervical cancer screening in 11,064 Chinese women

Over Expressed TKTL1, CIP-2A, and B-MYB Proteins in Uterine Cervix Epithelium Scrapings as Potential Risk Predictive Biomarkers in HR-HPV-Infected LSIL/ASCUS Patients

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