scholarly journals Multiple HPV 16 infection with two strains: a possible marker of neoplastic progression

2020 ◽  
Author(s):  
Maria Teresa Bruno ◽  
Guido Scalia ◽  
Nazario Cassaro ◽  
Sara Boemi

Abstract Background. We studied the cases of single and multiple HPV infection and analyzed the correlation with negative cases, and preneoplastic and neoplastic lesions of the uterine cervix with the aim of making a contribution to the prognostic factor under discussionMethods: 909 women undergoing second level screening because they had been positive at cervical cytology were enrolled. All the patients underwent colposcopy and cervical biopsy with viral genotyping. We divided mHPV infection based on the number of genotypes present: infections with 2 strains, 3 strains, 4 strains and 5 or more strains.Statistical analysis The analysis of the data was made using the χ2 test. Contingency tables were created to evaluate the correlation between single, multiple and CIN2+ infections. Values with p <0.05 were considered statistically significant.Results: The presence of genotype HPV16 in our study was associated with a 12 times greater risk of developing a high-grade lesion, OR = 12.70. The patients with single infections had the highest incidence of CIN2+ (34.1 %) with respect to those with multiple infections (10.6%).When we studied in the mHPV infection the prevalence of the combinations between the genotypes, we found that in mHPV16 infections, the combinations HPV16, 18 and HPV16, 31 were the most frequent (55.5%) in CIN3 lesion.ConclusionsOur results suggest that single HPV infections have a greater risk of developing SCC with respect to multiple infections. Multiple HPV infections are relevant only in the first phase of the lesion (CIN1-CIN2), while they are absent in carcinomas, where infections are of a single genotype. In particular, among multiple infections, HPV16 infection with 2 HR genotypes is associated significantly with CIN2 / CIN3 (21/30) and has 4 times greater risk of developing a high-grade lesion. Thus, it is probable that only specific combinations of HPV (HPV16,18 - HPV 16,31) can be associated with a clinically significant impact, while other combinations can simply be correlated because of a common infection or diagnostic method used. Therefore, multiple HPV16 infections with two high-risk genotypes is a major risk of CIN2/CIN3.

2020 ◽  
Author(s):  
Maria Teresa Bruno ◽  
Guido Scalia ◽  
Nazario Cassaro ◽  
Sara Boemi

Abstract Background. We studied the cases of single and multiple HPV infection and analyzed the correlation with negative cases, and preneoplastic and neoplastic lesions of the uterine cervix with the aim of making a contribution to the prognostic factor under discussionMethods: 909 women undergoing second level screening because they had been positive at cervical cytology were enrolled. All the patients underwent colposcopy and cervical biopsy with viral genotyping. We divided mHPV infection based on the number of genotypes present: infections with 2 strains, 3 strains, 4 strains and 5 or more strains.Statistical analysis The analysis of the data was made using the χ2 test. Contingency tables were created to evaluate the correlation between single, multiple and CIN2+ infections. Values with p <0.05 were considered statistically significant.Results: The presence of genotype HPV16 in our study was associated with a 12 times greater risk of developing a high-grade lesion, OR = 12.70. The patients with single infections had the highest incidence of CIN2+ (34.1 %) with respect to those with multiple infections (10.6%).When we studied in the mHPV infection the prevalence of the combinations between the genotypes, we found that in mHPV16 infections, the combinations HPV16, 18 and HPV16, 31 were the most frequent (55.5%) in CIN3 lesion.ConclusionsOur results suggest that single HPV infections have a greater risk of developing SCC with respect to multiple infections. Multiple HPV infections are relevant only in the first phase of the lesion (CIN1-CIN2), while they are absent in carcinomas, where infections are of a single genotype. In particular, among multiple infections, HPV16 infection with 2 HR genotypes is associated significantly with CIN2 / CIN3 (21/30) and has 4 times greater risk of developing a high-grade lesion. Thus, it is probable that only specific combinations of HPV (HPV16,18 - HPV 16,31) can be associated with a clinically significant impact, while other combinations can simply be correlated because of a common infection or diagnostic method used. Therefore, multiple HPV16 infections with two high-risk genotypes is a major risk of CIN2/CIN3.


2020 ◽  
Author(s):  
Maria Teresa Bruno ◽  
Guido Scalia ◽  
Nazario Cassaro ◽  
Sara Boemi

Abstract Background. We studied the cases of single and multiple HPV infection and analyzed the correlation with negative cases, and preneoplastic and neoplastic lesions of the uterine cervix with the aim of making a contribution to the prognostic factor under discussionMethods: 909 women undergoing second level screening because they had been positive at cervical cytology were enrolled. All the patients underwent colposcopy and cervical biopsy with viral genotyping. We divided mHPV infection based on the number of genotypes present: infections with 2 strains, 3 strains, 4 strains and 5 or more strains. Statistical analysis The analysis of the data was made using the χ2 test. Contingency tables were created to evaluate the correlation between single, multiple and CIN2+ infections. Values with p <0.05 were considered statistically significant.Results: The presence of genotype HPV16 in our study was associated with a 12 times greater risk of developing a high-grade lesion, OR = 12.70. The patients with single infections had the highest incidence of CIN2+ (34.1 %) with respect to those with multiple infections (10.6%).When we studied in the mHPV infection the prevalence of the combinations between the genotypes, we found that in mHPV16 infections, the combinations HPV16, 18 and HPV16, 31 were the most frequent (55.5%) in CIN3 lesion.ConclusionsOur results suggest that single HPV infections have a greater risk of developing SCC with respect to multiple infections. Multiple HPV infections are relevant only in the first phase of the lesion (CIN1-CIN2), while they are absent in carcinomas, where infections are of a single genotype. In particular, among multiple infections, HPV16 infection with 2 HR genotypes is associated significantly with CIN2 / CIN3 (21/30) and has 4 times greater risk of developing a high-grade lesion. Thus, it is probable that only specific combinations of HPV (HPV16,18 - HPV 16,31) can be associated with a clinically significant impact, while other combinations can simply be correlated because of a common infection or diagnostic method used. Therefore, multiple HPV16 infections with two high-risk genotypes is a major risk of CIN2/CIN3.


2020 ◽  
Author(s):  
Maria Teresa Bruno ◽  
Guido Scalia ◽  
Nazario Cassaro ◽  
Sara Boemi

Abstract Background : Some studies in the literature suggest a possible role of multiple HPV infections as a prognostic factor in the development and progression of cervical neoplasia. we studied the cases of single and multiple HPV infection and analyzed the correlation with negative cases, and preneoplastic and neoplastic lesions of the uterine cervix with the aim of making a contribution to the prognostic factor under discussion Methods: 921 women with clinical HPV manifestations were enrolled. Inclusion criteria were: positive at the cytology for HPV lesions, presence of preneoplastic and neoplastic lesions of the uterine cervix diagnosed by the histology examination All the patients underwent colposcopy and cervical biopsy with viral genotyping. The search for viral DNA was carried out using polymerase chain reaction. Genotype 16 is correlated with the majority of CIN2+; we divided the multiple HPV16 infections into “infections with 16 as the first genotype” (16mHPV) (e.g. HPV 16 , 31, 52) and into “ infections containing 16” (m16HPV) (e.g. HPV 31, 16 , 52), we then divided them based on the number of genotypes present: infections with 2 strains, 3 strains, 4 strains, and > 4 strains. Results: We analyzed the differences between single and multiple infections with HPV16, the patients with single infections had a higher incidence of CIN2+ (83.3%) with respect to those with multiple infections (71.4%). The 16mHPV infection was significative for CIN2/CIN3. When the prevalence of the combinations between the genotypes was studied, we found that in 16mHPV infection HPV16, 18 and HPV 16, 31 were the most common combinations of mHPV infection (50%) and the most frequent in CIN2/CIN3 The 16mHPV infection with 2 genotypes, with respect to the infections with 3 or more genotypes, was significative with an OR= 7.94 (IC% 2.55-24.73). Conclusions: Our results suggest that single HPV infections give a higher risk of SCC development with respect to multiple HPV infections. Among multiple infections, only 16mHPV infection with 2 genotypes is associated with CIN2/CIN3 in a significative way and it presents an 8 times greater risk of developing a high grade lesion.


2020 ◽  
Vol 96 (6) ◽  
pp. 457-463 ◽  
Author(s):  
Brandon L Guthrie ◽  
Anne F Rositch ◽  
Joy Alison Cooper ◽  
Carey Farquhar ◽  
Rose Bosire ◽  
...  

ObjectiveHIV infection increases the risk of high-grade cervical neoplasia and invasive cervical carcinoma. The study addresses the limited data describing human papillomavirus (HPV) infection and cervical neoplasia among HIV-infected women in HIV-discordant relationships in sub-Saharan Africa, which is needed to inform screening strategies.MethodsA cross-sectional study of HIV-infected women with HIV-uninfected partners was conducted to determine the distribution of type-specific HPV infection and cervical cytology. This study was nested in a prospective cohort recruited between September 2007 and December 2009 in Nairobi, Kenya. Cervical cells for HPV DNA testing and conventional cervical cytology were collected. HPV types were detected and genotyped by Roche Linear Array PCR assay.ResultsAmong 283 women, the overall HPV prevalence was 62%, and 132 (47%) had ≥1 high-risk (HR)-HPV genotype. Of 268 women with cervical cytology results, 18 (7%) had high-grade cervical lesions or more severe by cytology, of whom 16 (89%) were HR-HPV-positive compared with 82 (41%) of 199 women with normal cytology (p<0.001). The most common HR-HPV types in women with a high-grade lesion or more severe by cytology were HPV-52 (44%), HPV-31 (22%), HPV-35 (22%), HPV-51 (22%) and HPV-58 (22%). HR-HPV genotypes HPV-16 or HPV-18 were found in 17% of women with high-grade lesions or more severe. HR-HPV screening applied in this population would detect 89% of those with a high-grade lesion or more severe, while 44% of women with normal or low-grade cytology would screen positive.ConclusionHR-HPV prevalence was high in this population of HIV-infected women with an uninfected partner. Choice of screening for all HR genotypes versus a subset of HR genotypes in these HIV-infected women will strongly affect the performance of an HPV screening strategy relative to cytological screening. Regional and subpopulation differences in HR-HPV genotype distributions could affect screening test performance.


Author(s):  
Nithya Subbaiyan ◽  
Sabari Kasinathan

Background: Cancer of the cervix is a leading cause of morbidity and mortality among women worldwide. Therefore, to curb the disease, there is a need to develop a screening test that has good sensitivity and specificity. The aim is to compare the efficiency of Colposcopic Via, Vili, Liquiprep TM and conventional pap smear; as screening procedure for carcinoma cervix.Methods: This study was conducted in 100 women in the reproductive age. The pap smear and VIA are done in these cases. In positive cases, cervical biopsy and histopathological studies are done, the sensitivity and specificity of each test are determined and compared.Results: In this study, more cases belonged to 30 - 45 years age group. Among 100 women, 15% cases had high-grade lesion. Among high-grade lesions group, one case that is 6.7% had CIN 1, 73.3% had CIN2/3 and 3cases i.e., 20% had cervicitis. Among 100 women, 1% had ASCUS result, 10% belongs to HSIL group, 39% belongs to LSIL group and 2% had an unsatisfactory result.Conclusions: The lack of an effective and implementable screening programme lead to reporting of advanced cases of Ca Cervix. If detected at CIN or early Ca cervix stage, effective treatment can be provided with encouraging results. Therefore, effective and implementable Ca Cervix screening need to be provided in our country.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248639
Author(s):  
Camila Mareti Bonin-Jacob ◽  
Larissa Zatorre Almeida-Lugo ◽  
Marco Antonio Moreira Puga ◽  
Ana Paula Machado ◽  
Cacilda Tezelli Junqueira Padovani ◽  
...  

Persistent infection by high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer and its precursor lesions. While some cytokines help immune cells in virus clearance, others contribute to the persistence of infection and neoplastic progression. Here, the levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-10, IL-6, IL-4, and IL-2 were quantified in the serum and exfoliated cervical cells (ECCs) of patients with HR-HPV, and the presence of IL-6+ cells was investigated in uterine cervix biopsies. Cytokine levels in the serum and ECCs of 26 HR-HPV DNA-positive patients and 18 HPV DNA-negative patients were measured using flow cytometry. Fifteen uterine cervix biopsy samples embedded in paraffin were subjected to immunohistochemical analysis for the detection of IL-6+ cells. HR-HPV-positive patients showed increased IL-6 and IL-10 in the ECCs and serum, respectively. Compared with HPV DNA-positive patients, HPV DNA-negative patients had higher levels of IL-6 in ECCs. Patients with multiple infections of HPV had higher levels of IL-6 in their ECCs than those with a single infection. Immunostaining of uterine cervix biopsy samples revealed no differences in IL-6 expression between the different classes of histopathological lesions. However, differences were observed in the expression levels of IL-6 and IL-10 at the systemic and local levels in HR-HPV-positive patients without cervical lesions. Considering the functional characteristics of these cytokines, it can be inferred that such patients are prone to persistent HPV infection.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Lucia Oton-Gonzalez ◽  
John Charles Rotondo ◽  
Luca Cerritelli ◽  
Nicola Malagutti ◽  
Carmen Lanzillotti ◽  
...  

Abstract Background Killian polyp (KP) is a benign lesion that arises from the maxillary sinus. The etiology of KP is unknown. The aim of this study was to investigate the potential involvement of human papilloma- (HPV) and polyoma-viruses (HPyV) infections in the onset of KP. Methods DNA from antral (n = 14) and nasal (n = 14) KP fractions were analyzed for HPV and HPyV sequences, genotypes, viral DNA load and physical status along with expression of viral proteins and p16 cellular protein. Results The oncogenic HPV16 was detected in 3/14 (21.4%) antral KPs, whilst nasal KPs tested HPV-negative (0/14). The mean HPV16 DNA load was 4.65 ± 2.64 copy/104 cell. The whole HPV16 episomal genome was detected in one KP sample, whereas HPV16 DNA integration in two KPs. P16 mRNA level was lower in the KP sample carrying HPV16 episome than in KPs carrying integrated HPV16 and HPV- negative KPs (p< 0.001). None of the antral and nasal KP samples tested positive for HPyV DNA (0/28). Conclusions A fraction of KP tested positive for the oncogenic HPV16. HPV16 detection in the KP antral portion may be consistent with HPV16 infection derived from the maxillary sinus. HPV16 DNA integration represents a novel finding. Altogether, these data improve our knowledge on the association between KP and HPV infection, whereas it indicates that the KP onset is heterogeneous.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Severien Van Keer ◽  
Annina P. van Splunter ◽  
Jade Pattyn ◽  
Annemie De Smet ◽  
Sereina A. Herzog ◽  
...  

AbstractHost cell DNA methylation analysis in urine provides promising triage markers for women diagnosed with a high-risk (HR) human papillomavirus (HPV) infection. In this study, we have investigated a panel of six host cell methylation markers (GHSR, SST, ZIC1, ASCL1, LHX8, ST6GALNAC5) in cervicovaginal secretions collected within the first part of the urine void (FVU) from a referral population. Cytology, histology, and HPV DNA genotyping results on paired FVU and cervical samples were available. Urinary median methylation levels from HR-HPV (n = 93) positive women were found to increase for all markers with severity of underlying disease. Significantly elevated levels were observed for GHSR and LHX8 in relation to high-grade cervical intraepithelial neoplasia (CIN2 +; n = 33), with area under de curve values of 0.80 (95% Confidence Interval (CI) 0.59–0.92) and 0.76 (95% CI 0.58–0.89), respectively. These findings are the first to support the assertion that methylation analysis of host cell genes is feasible in FVU and holds promise as molecular, triage strategy to discern low- from high-grade cervical disease in HR-HPV positive women. Molecular testing on FVU may serve to increase cervical cancer screening attendance in hard-to-reach populations whilst reducing loss to follow-up and await further optimization and validation studies.


2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S163-S164
Author(s):  
K G Manjee ◽  
W G Watkin

Abstract Introduction/Objective Cervical biopsy is performed following an abnormal pap smear or positive HPV testing in an attempt to uncover clinically significant lesions [HSIL/invasive carcinoma (HSIL+)]. An excisional procedure is considered if biopsy confirms HSIL+. When preceded by pap smear of LSIL, ASCUS, NILM/HPV+ or persistent HPV, continued surveillance is recommended for biopsies showing no SIL or LSIL. In our laboratory, cervical biopsies are routinely sectioned at 3 levels. Deeper levels are often ordered when initial sections are non-diagnostic. p16 immunohistochemistry, with or without deeper levels, is often ordered to confirm HSIL, or to differentiate HSIL from mimics. In this study, we examine whether and in what clinical situations does obtaining additional levels uncover clinically significant lesions. Methods 430 cervical biopsies between January-May 2018, with recent cytology of LSIL, ASCUS or NILM/HPV+ were identified in the pathology database. HPV status (if known), final biopsy diagnosis and past history of LSIL/HSIL were recorded. For each biopsy, orders for additional levels and/or p16 immunohistochemistry were recorded resulting in 4 categories: C1-no additional levels or p16, C2-deeper only, C3-deeper+p16 and C4-p16 only. Final diagnoses were divided into HSIL+, LSIL and no SIL. Results There was no significant difference in prior history of LSIL/HSIL and HPV status between all categories. Biopsy results were as follows: HSIL+: 11/222 (5%) C1; 1/78 (1%) C2; 7/43 (16%) C3; 15/87 (17%) C4 LSIL: 91/222 (41%) C1; 7/78 (9%) C2; 16/43 (37%) C3; 35/87 (40%) C4 No SIL: 120/222 (54%) C1; 70/78 (90%) C2; 20/43 (46%) C3; 37/87 (42%) C4 The average number of additional levels in C2 and C3 was 3.8 and 1.8, respectively. Conclusion Deeper levels alone did not enhance the detection of HSIL+. Almost all LSIL/HSIL were detected when initial levels were diagnostic or suspicious and supported by p16 immunohistochemistry. 3 levels are adequate to detect clinically significant lesions.


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