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Research article
Multiple HPV 16 infection with two strains: a possible marker of neoplastic progression
Maria Teresa Bruno
Universita degli Studi di Catania
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1557-1538
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This work is licensed under a CC BY 4.0 License. Read Full License
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 discussion
Methods: 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.
Conclusions
Our 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.
Keywords
HPV infection, multiple HPV infection, CIN2+
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This preprint is under consideration at BMC Cancer. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Multiple HPV 16 infection with two strains: a possible marker of neoplastic progression
Maria Teresa Bruno
Universita degli Studi di Catania
Corresponding Author
ORCiD: https://orcid.org/0000-0003-1557-1538
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version 4
Posted 20 May, 2020
No community comments so far
Editor assigned
On 05 May, 2020
Editor invited
On 04 May, 2020
Submission checks complete
On 11 Mar, 2020
No comments provided
Editorial decision: Major revision
On 30 Apr, 2020
No comments provided
Editorial decision: Major revision
On 24 Apr, 2020
Editor assigned
On 23 Apr, 2020
Submission checks complete
On 22 Apr, 2020
Editor invited
On 22 Apr, 2020
No comments provided
Editorial decision: Major revision
On 27 Mar, 2020
Review #4 received
Received 27 Mar, 2020
Review #3 received
Received 20 Mar, 2020
Review #2 received
Received 20 Mar, 2020
Reviewer #3 agreed
On 20 Mar, 2020
Reviewer #4 agreed
On 20 Mar, 2020
Reviewer #2 agreed
On 19 Mar, 2020
Review #1 received
Received 19 Mar, 2020
Reviewers invited
Invitations sent on 17 Mar, 2020
Reviewer #1 agreed
On 17 Mar, 2020
Submission checks complete
On 12 Mar, 2020
Editor invited
On 12 Mar, 2020
Editor assigned
On 12 Mar, 2020
First submitted
On 10 Mar, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
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 discussion
Methods: 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.
Conclusions
Our 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.
Figure 1
Figure 2