Risk of high‐grade precancerous lesions and invasive cancers in high‐risk HPV‐positive women with normal cervix or CIN 1 at baseline—A population‐based cohort study

Mittal, Srabani; Basu, Partha; Muwonge, Richard; Banerjee, Dipanwita; Ghosh, Ishita; Sengupta, Mitali Mukherjee; Das, Pradip; Dey, Priatosh; Mandal, Ranajit; Panda, Chinmay Kumar; Biswas, Jaydip; Sankaranarayanan, Rengaswamy

doi:10.1002/ijc.30609

Cited by 46 publications

(30 citation statements)

References 28 publications

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“…We detected 48 HR-HPV-positive samples with apparent normal cytology, where 62.1% had multiple HR-HPV infections and 63.8% had a high viral load. A high viral load has previously been associated with the risk of persistent HPV infection [32]. We found that the patients with a persistent infection had a higher viral load at the time of the first sample collection, a finding that has been previously reported as a risk factor for persistent infection in other studies [33].…”

Section: Discussionsupporting

confidence: 83%

Multiple HPV Infections and Viral Load Association in Persistent Cervical Lesions in Mexican Women

Oyervides-Muñoz

Pérez-Maya

Sánchez‐Domínguez

et al. 2020

Viruses

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Persistent high-risk human papillomavirus (HR-HPV) infections play a major role in the development of invasive cervical cancer (CC), and screening for such infections is in many countries the primary method of detecting and preventing CC. HPV typing can be used for triage and risk stratification of women with atypical squamous cells of undetermined significance (ASC-US)/low-grade cervical lesions (LSIL), though the current clinical practice in Mexico is to diagnose CC or its preceding conditions mainly via histology and HR-HPV detection. Additional information regarding these HPV infections, such as viral load and co-infecting agents, might also be useful for diagnosing, predicting, and evaluating the possible consequences of the infection and of its prevention by vaccination. The goal of this follow-up hospital case study was to determine if HPV types, multiple HPV infections, and viral loads were associated with infection persistence and the cervical lesion grade. A total of 294 cervical cytology samples drawn from patients with gynecological alterations were used in this study. HPV types were identified by real-time PCR DNA analysis. A subset of HPV-positive patients was reevaluated to identify persistent infections. We identified HPV types 16, 18, and 39 as the most prevalent. One hundred five of the patients (59%) were infected with more than one type of HPV. The types of HPV associated with multiple HPV infections were 16, 18, and 39. In the follow-up samples, 38% of patients had not cleared the initially detected HPV infection, and these were considered persistent. We found here an association between multiple HPV infections and high viral loads with and infection persistence. Our findings suggest there are benefits in ascertaining viral load and multiple HPV infections status of HR-HPV infections for predicting the risk of persistence, a requirement for developing CC. These findings contribute to our understanding of HPV epidemiology and may allow screening programs to better assess the cancer-developing risks associated with individual HR-HPV infections.

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Section: Discussionsupporting

confidence: 83%

Multiple HPV Infections and Viral Load Association in Persistent Cervical Lesions in Mexican Women

Oyervides-Muñoz

Pérez-Maya

Sánchez‐Domínguez

et al. 2020

Viruses

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“…Interestingly, among women <30 years with normal cytology there was a lower sensitivity for the HPV‐mRNA test (80%) compared to the HPV‐DNA test (89%). It is tempting to speculate that the difference in sensitivity may reflect transient HPV‐infections only detectable by the HPV‐DNA test, as transient HPV infections decrease with increasing age of women . However, our observation does not affect our main conclusion that HPV mRNA testing is appropriate for HPV primary screening programs which start for women ≥30 years of age …”

Section: Discussionmentioning

confidence: 69%

“…It is tempting to speculate that the difference in sensitivity may reflect transient HPV-infections only detectable by the HPV-DNA test, as transient HPV infections decrease with increasing age of women. 16 However, our observation does not affect our main conclusion that HPV mRNA testing is appropriate for HPV primary screening programs which start for women ≥30 years of age. 3 Both AIS and the usual types of ADC are aetiologically related to infection with HPV.…”

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confidence: 58%

HPV‐mRNA and HPV‐DNA detection in samples taken up to seven years before severe dysplasia of cervix uteri

Forslund

Elfström

Lamin

et al. 2018

Intl Journal of Cancer

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Randomized clinical trials using human papillomavirus (HPV) DNA testing have found increased protection against cervical cancer and HPV-based screening is globally recommended for women ≥30 years of age. HPV-mRNA is a promising alternative target for cervical screening tests, but assessing equivalence requires longitudinal evaluation over at least the length of a screening interval. Our aim is to analyze the longitudinal sensitivity of HPV-mRNA and HPV-DNA in cervical samples taken up to 7 years before severe cervical intraepithelial neoplasia or worse (CIN3+). From a population-based cohort of 95,023 women in Sweden, cervical samples were frozen at -80°C between May 2007 and January 2012. Registry linkages identified that 1,204 of these women had CIN3+ 4 months to 7 years after enrolment. Baseline samples were analyzed for HPV-mRNA (Aptima, Hologic) and for HPV-DNA (Cobas 4800, Roche) and results from both tests obtained for 1,172 women. For both women <30 and ≥ 30 years, HPV-mRNA had similar sensitivity for CIN3+ as HPV-DNA (p = 0.0217 and p = 0.0123 in noninferiority testing for at least 90% relative sensitivity, respectively). Among women ≥30 years, the longitudinal sensitivities for CIN3+ occurring 5-7 years later were comparable [76.3% (95% CI: 65.8%-84.3%) and 82.5% (95% CI: 72.6%-89.4%)] as were the longitudinal negative predictive values for absence of CIN3+ [99.97% (95% CI: 99.95-99.98) and 99.98% (95% CI: 99.96-99.99)], for the HPV-mRNA and HPV-DNA test. In conclusion, HPV-mRNA testing has similar longitudinal sensitivity as HPV-DNA, implying that HPV-mRNA testing can safely be used for cervical screening.

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“…In contrast, persistent infection with high risk (HR)-HPV, including HPV16 and HPV18, can be followed by the integration of viral DNA into the host cell genome [ 5 ]. The probability of having persistent HR-HPV infection augments progressively with higher viral load [ 12 ] and it is favored by E5, E6 or E7 activities permitting HR-HPV escape from host immune surveillance. In particular, both the E5 and E7 proteins of HR-HPV can impair major histocompatibility complex (MHC)-restricted presentation of viral peptides to cytotoxic or helper T lymphocytes [ 13 , 14 ].…”

Section: Role Of the Hpv-e5 E6 And E7 Proteins In The Developmentmentioning

confidence: 99%

The Impact of Human Papilloma Viruses, Matrix Metallo-Proteinases and HIV Protease Inhibitors on the Onset and Progression of Uterine Cervix Epithelial Tumors: A Review of Preclinical and Clinical Studies

Barillari

Monini

Sgadari

et al. 2018

IJMS

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Infection of uterine cervix epithelial cells by the Human Papilloma Viruses (HPV) is associated with the development of dysplastic/hyperplastic lesions, termed cervical intraepithelial neoplasia (CIN). CIN lesions may regress, persist or progress to invasive cervical carcinoma (CC), a leading cause of death worldwide. CIN is particularly frequent and aggressive in women infected by both HPV and the Human Immunodeficiency Virus (HIV), as compared to the general female population. In these individuals, however, therapeutic regimens employing HIV protease inhibitors (HIV-PI) have reduced CIN incidence and/or clinical progression, shedding light on the mechanism(s) of its development. This article reviews published work concerning: (i) the role of HPV proteins (including HPV-E5, E6 and E7) and of matrix-metalloproteinases (MMPs) in CIN evolution into invasive CC; and (ii) the effect of HIV-PI on events leading to CIN progression such as basement membrane and extracellular matrix invasion by HPV-positive CIN cells and the formation of new blood vessels. Results from the reviewed literature indicate that CIN clinical progression can be monitored by evaluating the expression of MMPs and HPV proteins and they suggest the use of HIV-PI or their derivatives for the block of CIN evolution into CC in both HIV-infected and uninfected women.

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Risk of high‐grade precancerous lesions and invasive cancers in high‐risk HPV‐positive women with normal cervix or CIN 1 at baseline—A population‐based cohort study

Cited by 46 publications

References 28 publications

Multiple HPV Infections and Viral Load Association in Persistent Cervical Lesions in Mexican Women

Multiple HPV Infections and Viral Load Association in Persistent Cervical Lesions in Mexican Women

HPV‐mRNA and HPV‐DNA detection in samples taken up to seven years before severe dysplasia of cervix uteri

The Impact of Human Papilloma Viruses, Matrix Metallo-Proteinases and HIV Protease Inhibitors on the Onset and Progression of Uterine Cervix Epithelial Tumors: A Review of Preclinical and Clinical Studies

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