Lack of molecular mimicry between HPV vaccine L1 antigen and human proteins by a computational analysis

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Based on the molecular mimicry theory by Darja Kanduc, plaintiffs' attorneys argued that HPV vaccines could cause organ damage due to cross-reactive autoantibodies. Kauduc proposed a flawed hypothesis that molecular mimicry would induce cross-reactive antibodies even when only the portions of amino acid (AA)-sequences of the epitopes were identical between microbial and human proteins. Methods In this study, we conducted the same computational data analysis as Kanduc, using 22 linear epitopes (9–23 AA-length) of the HPV type 16 L1 protein (HPV16L1) registered in the database. Results We found that no human epitopes had identical AA-sequences to any HPV16L1 epitopes, demonstrating that HPV16L1 had no molecular mimicry with linear epitopes that have the potential to induce cross-reactive autoantibodies. On the other hand, we identified various numbers of human protein epitopes whose AA-sequences were partially identical with epitopes of HPV16L1, hepatitis B virus (HBV), and syncytial virus (RSV). We found that HPV16L1 had a smaller number of such proteins having “partial molecular mimicry” than HBV and RSV. Conclusions Our current in silico analysis provided no evidence that HPV vaccinations could induce cross-reactive autoantibodies. The flawed molecular mimicry data should not be used as a scientific basis for alleged HPV vaccine-induced adverse events. Amino Acid Sequences Autoimmunity Cross Reactions HANS Uterine Cervical Neoplasms Figures Figure 1 1 Introduction Cervical cancer is the fourth most common malignant neoplasm worldwide. In Japan, about 10,000 people were diagnosed with cervical cancer, among which 3000 people died, annually [ 1 ]. Persistent human papillomavirus (HPV) infection is the major cause of cervical cancer, of which HPV type 16 (HPV16) and HPV18 accounted for about 70% [ 2 ]. HPV vaccines contain a recombinant protein of the HPV L1 protein and an adjuvant. Bivalent HPV vaccines (2vHPV) have been developed for the prevention of HPV16 and HPV18 infections. A quadrivalent vaccine (4vHPV) can prevent infections caused by HPV6, HPV11, HPV16, and HPV18. Both 2vHPV and 4vHPV can prevent nearly 100% of HPV16 and HPV18 infections, as well as almost all precancerous lesions caused by HPV16 and HPV18 in uninfected individuals [ 3 , 4 ]. Recently, it has been reported that the efficacy of the nonavalent HPV vaccine (9vHPV) in preventing infections with HPV31, 33, 45, 52, and 58, in addition to the four HPV types included in the 4vHPV [ 5 ]. The World Health Organization has concluded that all three HPV vaccines (2vHPV, 4vHPV, and 9vHPV) had an excellent safety and efficacy profile and recommended that HPV vaccines be included in national immunization programs [ 6 ]. In Japan, HPV vaccinations began in 2010 and became routine in April 2013. In June 2013, however, widespread media coverage of "diverse symptoms," or a novel disease entity, “HPV vaccination-associated neuro-immunopathic syndrome (HANS),” characterized by widespread pain and neuro-psychological abnormalities, following HPV vaccinations, led to a suspension of proactive vaccination recommendations. The HPV vaccination coverage rate became less than 1% [ 7 ]. Later, national and international studies denied the causal relationship between HPV vaccinations and the "diverse symptoms" [ 8 ], which had resulted from other causes, including functional disorders, such as immunization stress-related reactions (ISRRs) [ 9 ]. Although the proactive recommendations of HPV vaccinations resumed in April 2022, the HPV vaccination rate in Japan remained low [ 10 ]. In Japan, there are ongoing HPV vaccine adverse event lawsuits alleging that HPV vaccinations caused various serious systemic and neurological sequelae. The outcome of the HPV vaccine lawsuits is expected to affect HPV vaccination coverage not only in Japan but also worldwide. Plaintiffs' lawyers argued that, since portions of amino acid (AA) sequences of HPV and human proteins are highly homologous, HPV vaccinations might induce autoantibodies that could cause organ damage, leading to autoimmune diseases and multiple sclerosis (MS) [ 11 , 12 , 13 ]. Clinically and experimentally, however, no studies have demonstrated the presence of such cross-reactive autoantibodies in human or animal sera following HPV vaccinations. In addition, increases in autoimmune diseases and any other diseases following HPV vaccinations have been denied, epidemiologically [ 14 ]. The plaintiff's legal team argued that, in theory, the HPV vaccinations could induce autoantibodies based on manuscripts by Darja Kanduc [ 11 ]. Kanduc compared the AA-sequences between all proteins of HPV16 (structural L1 and L2 and non-structural E1-E7 proteins) versus the human proteome. Kauduc claimed that large numbers of 7AA- or 8AA-length sequences, which were designated as “heptapeptide (or heptamer, 7-mer motif)” or “octapeptide,” respectively [ 15 ], and 5AA- or 6AA-length sequences (“pentapeptide, 5-mer motif” or “hexapeptide, 6-mer motif”) [ 16 ] were commonly present in HPV and human proteins. Kanduc’s data cannot be used as evidence that the HPV vaccine causes autoantibodies, since her manuscripts had the following scientific flaws. Although Kanduc compared AA-sequences of all HPV proteins with human proteins in her first report [ 15 ], the HPV vaccines contains only the HPV L1 protein, not the other HPV proteins (L2 and E1-E7). In addition, antibodies recognize and bind to specific AA sequences of the antigen, which is called an epitope. Although only the molecular mimicry between HPV L1 epitopes and host protein epitopes has the potential cross-reactive response, Kanduc compared the entire AA-sequences of HPV proteins and human proteomes, including non-epitope regions [ 16 ]. Later, Kanduc et al. compared a portion of the linear epitopes of HPV16 L1 protein (HPV16L1) with those of human proteins based on the erroneous hypothesis that if a partial sequence of the epitope matched a human protein, it could produce autoantibodies [ 17 ]. Immunologically, however, since an epitope is the smallest unit that reacts as an antigen to antibody binding, the discoveries of the similarities between parts of the epitope sequences and those of human epitopes, instead of the full-length sequence of epitopes, were irrelevant to cross-reactivities of anti-microbial antibodies to human proteins. In this study, we performed a computational analysis using the same methodology as Kanduc’s group. This study will help clarify the understanding of HPV vaccines by showing that the claim that HPV vaccines induce autoantibodies through molecular mimicry is incorrect. 2 Materials and Methods 2.1 Molecular mimicry analysis between the HPV16L1 and human epitopes Using the method described by Kanduc et al. [ 17 ], we identified the linear epitopes of the B cell receptor (antibody) against the HPV16 L1 in the Immune Epitope Database (IEDB) ( https://www.iedb.org/ ). In the IEDB, no L1 epitope of HPV type 18 was registered. Then, we compared the AA-sequences of HPV16 L1 epitopes of the human antibodies and the human protein epitopes of the human antibodies. The Basic Local Alignment Search Tool (BLAST) ( https://blast.ncbi.nlm.nih.gov/Blast.cgi?PAGE=Proteins ) was used to determine whether the same AA-sequences in the HPV16 L1 epitopes could be found in human antibody epitopes of human proteins as described previously by Kanduc et al. [ 16 ]. We examined not only the AA-sequences of the full length of the linear epitopes, but also the portions of AA-sequences of the epitopes from five AA-length (pentapeptide) to 27 AA-length [ 16 ]. 2.2 Molecular mimicry analysis using HBV and RSV We identified the linear epitopes of the full-length hepatitis B virus (HBV) [ 18 ] and respiratory syncytial virus (RSV) [ 19 ] on human B cell receptors in the IEDB. From the sequences of these HBV and RSV epitopes, we randomly generated five sets of the same numbers of AA-sequences as those generated from the HPV L1 epitopes: HBV sets 1–3 and RSV sets 1 and 2 ( Tables S1-5 , note: in RSV set 2, we were not able to make the same numbers, but smaller numbers of 10-peptide, 11-peptide, 12-peptide and 13-peptide). Then, using the BLAST, we determined the numbers of AA-sequences among the HBV and RSV epitopes, which were identical to those of human B cell epitopes. HBV epitopes were from four open reading frames (ORFs): large hepatitis B surface antigen (PreS1, PreS2, and HBs); pre-core/core ORF (HBc and HBe); HBx (protein X); and DNA polymerase [ 20 ]. RSV epitopes were from F protein, G protein, N protein, and P protein [ 21 ]. 2.3 Molecular mimicry analysis using random AA-sequences and gene ontology analysis We generated four sets of random AA-sequences (Random array sets 1–4, Tables S6-9 ), which contained the same AA-length and sequence numbers as those of HPV16L1, using Excel's random number generator. We used the BLAST to identify the AA-sequences that matched human protein epitopes. We also conducted gene ontology analysis using the list of identified human proteins that shared the AA-sequences with AA-sequence of Random array sets, using the Gene Ontology Resource ( https://geneontology.org/ ). 2.4 Statistical analysis Welch's t -test was used to compare the number of human proteins sharing the same AA-sequences with virus-derived and random sequences. Statistical analysis was performed using Prism 10.4 (GraphPad Software, Boston, MA). 3 Results 3.1 AA-sequence comparison between HPV and human epitopes To analyze molecular mimicry between HPV L1 and human proteins, we used 22 linear epitopes of HPV16L1, whose AA-sequence lengths ranged from 9 to 27, registered in the IEDB; the AA-sequence lengths of the epitopes ranged from 9 to 27 (Table 1 ). We found that no human proteins had identical sequences to the entire AA-sequences of the 22 linear epitopes. Thus, this computational analysis provided evidence that no antibodies against any epitopes of HPV16L1 would function as autoantibodies against human proteins. Table 1 Linear epitopes of HPV16 L1 protein HPV epitope ID Epitope AA length 5-peptide 6-peptide 7-peptide 8-peptide 9-peptide 10-peptide 11-peptide 12-peptide 13-peptide References and DOI 109332 IHSMNSTIL 9 5 4 3 2 1 - - - - Zavaleta R et al. J Gen Virol 2004 10.1099/vir.0.80077-0 110602 GLKAKPKFTLGKRKATPTT 19 15 14 13 12 11 10 9 8 7 Le Cann P et al. J Med Virol 1995 10.1002/jmv.1890450410 110651 LCLIGCKPPIGEHWGKGSP 19 15 14 13 12 11 10 9 8 7 Lenner P et al. Cancer Immunol 1995 10.1007/BF01517352 110652 LCLIGCKPPIGEHWGKGSPC 20 16 15 14 13 12 11 10 9 8 Dillner J et al. Int J Cancer. 1990 10.1002/ijc.2910450326 110733 VGENVPDDLYIKGSG 15 11 10 9 8 7 6 5 4 3 Le Cann P et al. J Med Virol 1995 10.1002/jmv.1890450410 110825 EDTYRFVTSQAIACQKHTPPA 21 17 16 15 14 13 12 11 10 9 Leon S et al. Sex Transm Dis. 2009 10.1097/OLQ.0b013e318195762c 110863 GLKAKPKFTLGKRKATPTTS 20 16 15 14 13 12 11 10 9 8 Cason J et al. Int J Cancer. 1992 10.1002/ijc.2910500304 110872 GSGSTANLASSNYFP 15 11 10 9 8 7 6 5 4 3 110898 IACQKHTPPAPKEDPLKKYTFWEVNLK 27 23 22 21 20 19 18 17 16 15 Sharma BK et al. Eur J Cancer. 1996 10.1016/0959–8049(96)00005–6 110938 LYIKGSGSTANLASSNYFPT 20 16 15 14 13 12 11 10 9 8 Leon S et al. Sex Transm Dis. 2009 10.1097/OLQ.0b013e318195762c 110965 PNNNKILVPKVSGLQYRVFR 20 16 15 14 13 12 11 10 9 8 111088 ACQKHTPPAPKEDDPLKKYT 20 16 15 14 13 12 11 10 9 8 Dillner J et al. Int J Cancer. 1990 10.1002/ijc.2910450326 111450 KGSPCTNVAVNPGDCPPLEL 20 16 15 14 13 12 11 10 9 8 111581 NGICWGNQLFVTVVDTTRST 20 16 15 14 13 12 11 10 9 8 111583 NKFGFPDTSFYNPDTQRLVW 20 16 15 14 13 12 11 10 9 8 111585 NKSEVPLDICTSICKYPDYI 20 16 15 14 13 12 11 10 9 8 111890 VDNRECISMDYKQTQLCLIG 20 16 15 14 13 12 11 10 9 8 111915 VHTGFGAMDFTTLQANKSEV 20 16 15 14 13 12 11 10 9 8 175631 PLGVGISGHPLLNKLDDTEN 20 16 15 14 13 12 11 10 9 8 Yokomine M et al. Exp Ther Med. 2017 10.3892/etm.2017.4150 175636 PTPSGSMVTSDAQIFNKPYW 20 16 15 14 13 12 11 10 9 8 175665 VTSDAQIFNKPYWLQRAQGH 20 16 15 14 13 12 11 10 9 8 604717 TSDAQIFNKP 10 6 5 4 3 2 1 - - - Total sequence number 327 305 283 261 239 217 196 176 156 Subtracted total sequence number* = Total sequence number – overlapped sequence number 248 237 225 211 196 181 167 152 137 *, Subtracted total sequence number (= the precise total sequence number) was determined by subtracting the number of overlapped AA sequences among all AA sequences from the total sequence number. For example, the 3rd ID 110651 and the 4th ID 110652 were almost identical except for the 3rd ID had only one additional AA; 19 AA sequences were overlapped in two IDs. The 10-AA length epitope of the last ID 604717 was included in the two preceding ID 175636 and ID 175665. Subtracting these duplicate sequences yields the precise total number. Next, using the same approach as described by Kanduc [ 11 ], we examined the number of human proteins that share the portion of the AA-sequences of the HPV16L1 epitopes, although sharing the portion of AA-sequences of the HPV16L1 epitopes with human protein epitopes alone does not result in the production of cross-reactive autoantibodies. For example, when we analyzed an AA-sequence identity of one 9-mer HPV16L1 epitope, IHSMNSTIL (Epitope ID 109332, Table 1 ), to the human epitopes at the consecutive seven AA-sequence level, which was called “heptapeptide,” “heptamer,” or “7-mer motif” by Kanduc [ 15 ], one can identify three heptapeptides, each peptide of which was offset by one residue, overlapping by six residues: i.e., 1) IHSMNST, 2) HSMNSTI, and 3) SMNSTIL. Using all the AA-sequences of the 22 linear epitopes, consisting of 9–27 AA-sequences, we were able to generate 248 pentapeptides (5AA-length). Then, using the BLAST search, we found that 1281 human protein epitopes shared at least one of these 248 pentapeptides (Table 2 ). Using the same method, we generated 237 hexapeptides (6AA-length) from the AA-sequences of the 22 epitopes; 106 human proteins shared at least one of these hexapeptides (Table 2 ). Similarly, 225 heptapeptides (7AA-length) were generated from the 22 epitopes shared with 16 human proteins; 211 octapeptides (8AA-length) shared with two human proteins; 196 nonapeptides (9AA-length) shared with two human proteins. No human protein had a sequence that was identical to the AA-sequence of HPV16L1 in 10AA or more than 10AA-length (Table 2 ). Table 2 Number of human epitope AA sequences identical to viral epitope AA sequences Virus Viral protein AA length (number of AA sequences) 5-peptide 6-peptide 7-peptide 8-peptide 9-peptide 10-peptide 11-peptide 12-peptide 13-peptide (248) (237) (225) (211) (196) (181) (167) (152) (137) HPV HPV16 L1 1281 106 16 2 2 0 0 0 0 HBV Set 1 Large hepatitis B surface antigen 1695 127 16 5 3 0 0 0 0 core protein HBx Set 2 Large hepatitis B surface antigen 1549 104 17 5 4 1 0 0 0 core protein HBx Set 3 Large hepatitis B surface antigen 1667 167 27 16 9 0 0 0 0 core protein HBx DNA polymerase RSV Set 1 G protein 1491 108 19 6 4 1 0 0 0 N protein F protein Set2 G protein 1720 117 24 12 7 4 1 1 0 N protein F protein P protein Random array Set 1 Not applicable 825 50 8 5 1 0 0 0 0 Set 2 972 60 13 4 3 1 0 0 0 Set 3 578 28 2 1 0 0 0 0 0 Set 4 649 39 10 2 0 0 0 0 0 3.2 HBV and RSV epitopes had larger numbers of AA-sequence homology with human epitopes than HPV epitopes There were 249 linear epitopes registered in the IEDB that used the full-length HBV protein as an antigen. From these, we randomly selected epitopes consisting of 9–27 AAs. From these epitopes, we generated the same number of AA-sequences as from the HPV16L1 epitopes, namely 248 pentapeptides (5AA-length); 237 hexapeptides (6AA-length); heptapeptides (7AA-length); 211 octapeptides (8AA-length); 196 nonapeptides (9AA-length); 181 10-peptides; 167 11-peptides; 176 12-peptides; and 138 13-peptides. Then, we generated three sets of these AA-sequence groups (HBV sets 1, 2, and 3) and examined the number of human proteins sharing these AA-sequences in HBV sets 1, 2, and 3 (Table 2 , Tables S1-3 ). Similarly, 159 linear epitopes were registered in the IEDB for the full-length human RSV protein. We followed the same approach for RSV as we did for HBV, creating two sets of groups of AA-sequences (RSV sets 1 and 2) and determining the number of human proteins that contained these AA-sequences (Table 2 , Tables S4-5 ). We compared the shared AA-sequence numbers at 5AA-, 6AA-, 7AA-, 8AA-, 9AA-, and 10AA-length levels. We found that the shared AA-sequence numbers in HPV epitopes were lower than those of HBV and RSV epitopes at all AA-length levels. 3.3 Viral epitopes had more shared AA-sequences with human epitopes than random AA-sequences We also randomly generated 9–27 AA-length sequences, from which we generated four sets of 5–13 AA-sequences (Random array sets 1, 2, 3, and 4) to determine the numbers of human epitope sequences identical to these random AA-sequences (Table 2 , Tables S6-9 ). When comparing the number of matching human epitopes for the three viral epitopes (HPV, HBV, and RSV combined) and for the Random array sets, the former were more common for penta-, hexa-, hepta-, octa- and nonapeptides (5 to 9 AA-length peptides). For example, at pentapeptide (5AA-length peptide) level, HPV had 1281; HBV sets 1–3 had 1549 to 1695; RSV sets 1–2 had 1491 to 1720; and Random array sets 1–4 had 825 to 972 pentapeptides commonly found in human protein epitopes (Table 2 , Fig. 1 ). Statistically, the mean numbers of the common AA-sequences ± standard error of the mean (SEM) were as follows (Fig. 1 ): 5AA-length, viral epitopes 1567.2 ± 67.7, random array, 756.0 ± 88.8, P < 0.001; 6AA-length, viral epitopes 121.5 ± 9.7, random array 44.3 ± 6.9, P < 0.001; 7AA-length, viral epitopes 19.8 ± 1.9 random array 8.3 ± 2.3, P < 0.01; 8AA-length, viral epitopes 7.7 ± 2.1, random array 3.0 ± 0.9, P < 0.1; and 9AA-length, viral epitopes 4.8 ± 1.1, random array 1.0 ± 0.7, P < 0.05. The numbers of matching human proteins for AAs derived from HPV16L1 epitopes were lower than for AAs derived from HBV and RSV epitopes. For example, the numbers of shared AA sequences at the 8AA level were as follows: HPV16L1, 2; HBV sets 1–3, 5 to 16; RSV sets 1–2, 6 and 12; and Random array sets 1–4, 1 to 5. When the length of the AAs was ten or more (where the specificity was high), there was no difference between combined virus epitope sequences versus the Random array sets. (Fig. 1 , Table 2 ) (The mean common AA-sequence number ± SEM: 10AA-length, viral epitopes 1.0 ± 0.63, random array 0.3 ± 0.3, P = 0.31). Lastly, we conducted gene ontology analysis using human protein epitopes sharing 5 to 11 AA-sequences with HPV16L1, HBV (sets 1–3), and RSV (sets 1–2) epitopes, and four sets of random array sequences. We found that there was no statistically significant enriching gene ontology term in the human proteins sharing with any three viral epitope groups or Random array sets. 4 Discussion Theoretically, when an in silico computational analysis shows that the full-length AA-sequences of the microbial epitopes are identical to a human protein epitope (i.e., having molecular mimicry), the microbial proteins have a potential to induce cross-reactive autoantibody production following microbial infections or vaccinations. On the other hand, when the analysis shows that only a portion of the epitope shared AA-sequences with host proteins, such “partial" molecular mimicry alone likely does not result in the production of cross-reactive antibodies. In our study, using the same approach as Kanduc’s group [ 17 ], we examined the antibody epitopes of HPV16L1 and found that none of the entire AA-sequences of the 22 linear epitopes (Table 1 ) were identical to any AA-sequences of human protein epitopes. Our result was consistent with findings by Kanduc’s group [ 12 , 17 ], who showed that there were no human protein epitopes identical to the HPV16L1 epitopes, although Kanduc’s group has never emphasized these crucial findings. In this study, we also showed the number of human proteins that had partial AA-sequence similarities to HPV16L1 epitopes. We found that HPV16L1 had fewer partial AA-sequence similarities than HBV and RSV epitopes. Although such “partial” molecular mimicry is irrelevant to the induction of cross-reactive autoantibodies, our results demonstrated that HPV16L1 epitopes were not unique in having a certain number of partial AA-sequence similarities with human protein epitopes, compared with other viral protein epitopes. We also demonstrated that viral protein epitopes (HPV16L1, HBV, and RSV) had more partial AA-sequence similarities with human protein epitopes than randomly generated AA sequences (i.e., Random array sets 1–4) (Fig. 1 ). Despite the evolutionary distance, humans and viruses may share specific sequence features that are biologically relevant for protein formation. On the other hand, for HPV16L1 epitope sequences, concordance with human proteins was equivalent to random sequences for AA-sequences of eight or more. Thus, human proteins did not have a highly specific match with the HPV16 L1 epitope sequences, although identical AA-sequences were commonly found at shorter AA-length levels (Fig. 1 ). Epidemiologically, HPV vaccinations have been demonstrated not to increase the incidence of immune-mediated diseases or any diseases [ 22 , 23 ]. Experimentally, no researcher, including Kanduc's group, has ever demonstrated cross-reactivity between the HPV L1 protein and human tissues/proteins by enzyme-linked immunosorbent assay (ELISA) or other methods using anti-HPV sera, anti-HPV L1 antibodies, or autoantibodies [ 11 , 24 ]. Clinically, no studies have shown antibody deposition in the organs, increased autoantibody production, or efficacy of immunotherapies in alleged patients with HANS. It is now widely accepted in the scientific community that there is no point in suggesting the risk of autoimmune diseases by demonstrating the sharing of short peptide sequences by in silico analysis without supporting epidemiological data or experimental evidence [ 25 , 26 , 27 , 28 ]. Kanduc et al. performed computational analyses on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, using the same computational approach in their HPV vaccine studies, and reported that the SARS-CoV-2 vaccines could be dangerous due to the presence of 5–7 AA-sequences shared between SARS-CoV-2 and human proteins [ 29 , 30 , 31 , 32 ]. Kanduc’s group also reported that vaccines against meningococcal B [ 33 ], diphtheria toxin [ 34 ], RSV [ 35 ], and HBV [ 12 , 36 ] could pose risks due to the presence of 5–7 shared AA-sequences with human proteins; some of the claims made by anti-vaccine advocates were based on these studies. None of these studies, however, experimentally tested whether vaccine-induced antibodies could cross-react with the plausible microbial epitopes or damage/kill the potential target human cell types/organs. As described above, the mere observation that certain AA-sequences of microorganisms have similarities to human proteins should not be used as a scientific basis for asserting vaccine risks. Adverse events following vaccination should be carefully and scientifically evaluated. Lawsuits and claims of vaccine-associated adverse events based on a scientifically flawed hypothesis can leave suffering people with unresolved clinical signs/symptoms after HPV vaccinations and may pose a baseless health concern in the general public, reducing the vaccination coverage rate. In conclusion, we demonstrated that the identical AA-sequences to full-length HPV16L1 epitopes were not present among the human protein epitopes. We also demonstrated that HPV16L1 epitopes had fewer partial AA-sequence similarities than HBV and RSV epitopes. Therefore, it is incorrect to assert the risk of HPV vaccinations based on common AA-sequences in the HPV vaccines and human protein epitopes. Declarations Acknowledgments: We thank members of the Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Fumitaka Sato and Sandesh Rimal of the Department of Microbiology, Kindai University Faculty of Medicine, and Ah-Mee Park of the Department of Arts and Sciences, Kindai University Faculty of Medicine. Funding Information Supported by the Grant-in-Aid for Scientific Research KAKENHI from the Japan Society for the Promotion of Science (JSPS), JP23K08901 (R.S.), and JP22K18378/JP23K08901/JP24K10163 (I.T.), the Kindai University Research Enhancement Grant KD2506 (I.T.). Conflict of Interest N.M. received lecture fees from AstraZeneca, Takeda Pharmaceutical, MSD, and Eisai, and research grants from AstraZeneca and Eisai. N.M. is an outside director of Takara Bio Inc. Other authors declare no conflicts of interest. Ethics Statement Approval of the research protocol by an Institutional Reviewer Board: N/A Informed Consent: N/A Registry and the Registration No. of the study/trial: N/A Animal Studies: N/A Author Contributions N.M. and I.T. conceived of and supervised the project. N.M. and K.N. designed the experiments. K.N. and N.M. conducted the experiments. K.N. and I.T. wrote the manuscript. K.S., R.S., and N.M. aided in the experiments and manuscript preparation. All authors have read and agreed to the published version of the manuscript. References Nakai H, Higashi T, Kakuwa T, Matsumura N (2024) Trends in gynecologic cancer in Japan: incidence from 1980 to 2019 and mortality from 1981 to 2021. Int J Clin Oncol 29(4):363–371. https://doi.org/10.1007/s10147-024-02473-8 Kusakabe M, Taguchi A, Sone K, Mori M, Osuga Y (2023) Carcinogenesis and management of human papillomavirus-associated cervical cancer. 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Am J Transpl 24(6):897–904. https://doi.org/10.1016/j.ajt.2024.02.003 Seeger C, Zoulim F, Mason WS (2022) Hepadnaviridiae. In: Howley PM, Knipe DM (eds) Fields Virology Volume 2: DNA Viruses, 7th edn. Wolters Kuwer, Philadelphia, PA, pp 641–682 Buchhoz UJ, Anderson LJ, Collins PL, Mejias A (2023) Respiratory syncytial virus and metapneumovirus. In: Howley PM, Knipe DM (eds) Fields Virology Volume 3: RNA Viruses, 7th edn. Wolters Kuwer, Philadelphia, PA, pp 267–317 Scheller NM, Svanström H, Pasternak B et al (2015) Quadrivalent HPV vaccination and risk of multiple sclerosis and other demyelinating diseases of the central nervous system. JAMA 313(1):54–61. https://doi.org/10.1001/jama.2014.16946 Meggiolaro A, Migliara G, Torre GL (2018) Association between human papilloma virus (HPV) vaccination and risk of multiple sclerosis: A systematic review. Hum Vaccin Immunother 14(5):1266–1274. https://doi.org/10.1080/21645515.2017.1423155 Matsumura N, Shiro R, Tsunoda I (2023) Critical evaluation on roles of macrophagic myofasciitis and aluminum adjuvants in HPV vaccine-induced adverse events. Cancer Sci 114(4):1218–1228. https://doi.org/10.1111/cas.15714 Hecker M, Fitzner B, Wendt M et al (2016) High-density peptide microarray analysis of IgG autoantibody reactivities in serum and cerebrospinal fluid of multiple sclerosis patients. Mol Cell Proteom 15(4):1360–1380. https://doi.org/10.1074/mcp.M115.051664 Prinz JC (2023) Immunogenic self-peptides - the great unknowns in autoimmunity: Identifying T-cell epitopes driving the autoimmune response in autoimmune diseases. Front Immunol 13:1097871. https://doi.org/10.3389/fimmu.2022.1097871 Fehringer M, Vogl T (2025) Molecular mimicry in the pathogenesis of autoimmune rheumatic diseases. J Transl Autoimmun 10:100269. https://doi.org/10.1016/j.jtauto.2025.100269 Megremis S, Walker TDJ, He X et al (2021) Analysis of human total antibody repertoires in TIF1γ autoantibody positive dermatomyositis. Commun Biol 4(419). https://doi.org/10.1038/s42003-021-01932-6 Kanduc D, Shoenfeld Y (2020) Molecular mimicry between SARS-CoV-2 spike glycoprotein and mammalian proteomes: implications for the vaccine. Immunol Res 68:310–313. https://doi.org/10.1007/s12026-020-09152-6 Dotan A, Muller S, Kanduc D, David P, Halpert G, Shoenfeld Y (2021) The SARS-CoV-2 as an instrumental trigger of autoimmunity. Autoimmun Rev 20(4):102792. https://doi.org/10.1016/j.autrev.2021.102792 Kanduc D (2021) From anti-SARS-CoV-2 immune response to the cytokine storm via molecular mimicry. Antibodies (Basel) 10(4):36. https://doi.org/10.3390/antib10040036 Kanduc D (2023) Exposure to SARS-CoV-2 and infantile diseases. Glob Med Genet 10(2):072–078. https://doi.org/10.1055/s-0043-1768699 Kanduc D (2023) Molecular mimicry between meningococcal B factor H-binding protein and human proteins. Glob Med Genet 10(4):311–314. https://doi.org/10.1055/s-0043-1776985 Bavaro SL, Kanduc D (2011) Pentapeptide commonality between Corynebacterium diphtheriae toxin and the Homo sapiens proteome. Immunotherapy 3(1):49–58. https://doi.org/10.2217/imt.10.83 Kanduc D (2023) Molecular mimicry between respiratory syncytial virus F antigen and the human proteome. Glob Med Genet 10(01):19–21. https://doi.org/10.1055/s-0043-1761489 Ricco R, Kanduc D (2010) Hepatitis B virus and Homo sapiens proteome-wide analysis: A profusion of viral peptide overlaps in neuron-specific human proteins. Biologics 2010:4:75–81. https://doi.org/10.2147/btt.s8890 Supplementary Files IJCOsup.table19.xlsx Cite Share Download PDF Status: Published Journal Publication published 08 Jan, 2026 Read the published version in International Journal of Clinical Oncology → Version 1 posted Reviewers agreed at journal 18 Sep, 2025 Reviewers invited by journal 17 Sep, 2025 Editor assigned by journal 17 Sep, 2025 First submitted to journal 13 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7609715","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":516794444,"identity":"a8bdf7e3-e3f7-4d23-9509-6f76f59ded01","order_by":0,"name":"Kazuhiro Nishioka","email":"data:image/png;base64,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","orcid":"https://orcid.org/0009-0000-0431-0573","institution":"Kindai University Nara Hospital: Kinki Daigaku Igakubu Nara Byoin","correspondingAuthor":true,"prefix":"","firstName":"Kazuhiro","middleName":"","lastName":"Nishioka","suffix":""},{"id":516794445,"identity":"5c2c6026-96c7-4d01-8684-b5f6ff3d8796","order_by":1,"name":"Kentaro Sekiyama","email":"","orcid":"","institution":"Kindai University Nara Hospital: Kinki Daigaku Igakubu Nara Byoin","correspondingAuthor":false,"prefix":"","firstName":"Kentaro","middleName":"","lastName":"Sekiyama","suffix":""},{"id":516794446,"identity":"a63e76f8-4c99-4ef5-b0d8-0a82e3d39dd5","order_by":2,"name":"Reona Shiro","email":"","orcid":"","institution":"Kindai University Nara Hospital: Kinki Daigaku Igakubu Nara Byoin","correspondingAuthor":false,"prefix":"","firstName":"Reona","middleName":"","lastName":"Shiro","suffix":""},{"id":516794447,"identity":"d27e6002-b12f-4e04-a750-0000a467d6bf","order_by":3,"name":"Ikuo Tsunoda","email":"","orcid":"https://orcid.org/0000-0003-1798-714X","institution":"Kindai University Faculty of Medicine Graduate School of Medical Sciences: Kinki Daigaku Igakubu Daigakuin Igaku Kenkyuka","correspondingAuthor":false,"prefix":"","firstName":"Ikuo","middleName":"","lastName":"Tsunoda","suffix":""},{"id":516794448,"identity":"b4f0351a-9380-4a81-91ea-64aef5f293e9","order_by":4,"name":"Noriomi 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17:43:55","extension":"xml","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":844,"visible":true,"origin":"","legend":"","description":"","filename":"IJCOD2501117Import.xml","url":"https://assets-eu.researchsquare.com/files/rs-7609715/v1/13807bfdf2cdd69d8a4597e1.xml"},{"id":92437795,"identity":"8ea619a8-b1d3-43af-86b4-961b5d853fc9","added_by":"auto","created_at":"2025-09-29 17:35:55","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":123194,"visible":true,"origin":"","legend":"","description":"","filename":"IJCOD25011170enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7609715/v1/0c60187da76fed445cc1ddff.xml"},{"id":92437800,"identity":"643b6427-15f6-4d1f-9de4-4647170f425a","added_by":"auto","created_at":"2025-09-29 17:35:57","extension":"tif","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":526596,"visible":true,"origin":"","legend":"","description":"","filename":"IJCOFig.1.tif","url":"https://assets-eu.researchsquare.com/files/rs-7609715/v1/96caa2dc07db4717f8c0c255.tif"},{"id":92437799,"identity":"dc32bb6a-a813-45b0-84eb-05ff99c5d3e3","added_by":"auto","created_at":"2025-09-29 17:35:57","extension":"xml","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":120811,"visible":true,"origin":"","legend":"","description":"","filename":"IJCOD25011170structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7609715/v1/5149e464098dc7902d633931.xml"},{"id":92437796,"identity":"89d28f6e-603f-4ab3-bdcc-231f6c06c123","added_by":"auto","created_at":"2025-09-29 17:35:55","extension":"html","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":130176,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7609715/v1/dc69df46231c5e2f93d19966.html"},{"id":92437789,"identity":"098ce44e-430e-4e2e-98fe-4cb9ebde0bf3","added_by":"auto","created_at":"2025-09-29 17:35:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":62186,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of the numbers of human amino acid (AA) sequences identical to viral AA-sequences or random array sequences at 5-peptide (pentapeptide), 6-peptide (hexapeptide), 7-peptide (heptapeptide), 8-peptide (octapeptide), 9-peptide (nonapeptide), or 10-peptide levels. We determined the shared AA-sequence numbers using the epitope data of human papillomavirus (HPV) 16 L1 (closed circle), hepatitis B virus (HBV) sets 1 to 3 (closed square), respiratory syncytial virus (RSV) sets 1 and 2 (closed triangle), and Random array sets 1 to 4 (open circle). At all AA-length levels, the shared AA-sequence numbers in HPV epitopes were lower than those of HBV and RSV epitopes. Welch's \u003cem\u003et\u003c/em\u003e-test was used to compare the numbers of human protein epitopes sharing the same AA-sequences with combined virus epitopes (HPV, HBV, and RSV) versus Random array sets 1 to 4.\u003c/p\u003e","description":"","filename":"OnlineIJCOFig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-7609715/v1/459bf97cd5a9750fd7e5f983.png"},{"id":100069372,"identity":"26fa2df2-c212-4420-8471-e592dac70149","added_by":"auto","created_at":"2026-01-12 16:13:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1145671,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7609715/v1/b83746ca-f5eb-45e3-ab17-5b398596ea51.pdf"},{"id":92437792,"identity":"c6256a8f-5ee8-4654-bdff-23881e08ec95","added_by":"auto","created_at":"2025-09-29 17:35:55","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":40639,"visible":true,"origin":"","legend":"","description":"","filename":"IJCOsup.table19.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7609715/v1/5616253da86f8820b38cff24.xlsx"}],"financialInterests":"","formattedTitle":"\u003cp\u003eLack of molecular mimicry between HPV vaccine L1 antigen and human proteins by a computational analysis\u003c/p\u003e","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eCervical cancer is the fourth most common malignant neoplasm worldwide. In Japan, about 10,000 people were diagnosed with cervical cancer, among which 3000 people died, annually [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Persistent human papillomavirus (HPV) infection is the major cause of cervical cancer, of which HPV type 16 (HPV16) and HPV18 accounted for about 70% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. HPV vaccines contain a recombinant protein of the HPV L1 protein and an adjuvant. Bivalent HPV vaccines (2vHPV) have been developed for the prevention of HPV16 and HPV18 infections. A quadrivalent vaccine (4vHPV) can prevent infections caused by HPV6, HPV11, HPV16, and HPV18. Both 2vHPV and 4vHPV can prevent nearly 100% of HPV16 and HPV18 infections, as well as almost all precancerous lesions caused by HPV16 and HPV18 in uninfected individuals [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Recently, it has been reported that the efficacy of the nonavalent HPV vaccine (9vHPV) in preventing infections with HPV31, 33, 45, 52, and 58, in addition to the four HPV types included in the 4vHPV [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The World Health Organization has concluded that all three HPV vaccines (2vHPV, 4vHPV, and 9vHPV) had an excellent safety and efficacy profile and recommended that HPV vaccines be included in national immunization programs [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn Japan, HPV vaccinations began in 2010 and became routine in April 2013. In June 2013, however, widespread media coverage of \"diverse symptoms,\" or a novel disease entity, \u0026ldquo;HPV vaccination-associated neuro-immunopathic syndrome (HANS),\u0026rdquo; characterized by widespread pain and neuro-psychological abnormalities, following HPV vaccinations, led to a suspension of proactive vaccination recommendations. The HPV vaccination coverage rate became less than 1% [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Later, national and international studies denied the causal relationship between HPV vaccinations and the \"diverse symptoms\" [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], which had resulted from other causes, including functional disorders, such as immunization stress-related reactions (ISRRs) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Although the proactive recommendations of HPV vaccinations resumed in April 2022, the HPV vaccination rate in Japan remained low [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn Japan, there are ongoing HPV vaccine adverse event lawsuits alleging that HPV vaccinations caused various serious systemic and neurological sequelae. The outcome of the HPV vaccine lawsuits is expected to affect HPV vaccination coverage not only in Japan but also worldwide. Plaintiffs' lawyers argued that, since portions of amino acid (AA) sequences of HPV and human proteins are highly homologous, HPV vaccinations might induce autoantibodies that could cause organ damage, leading to autoimmune diseases and multiple sclerosis (MS) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Clinically and experimentally, however, no studies have demonstrated the presence of such cross-reactive autoantibodies in human or animal sera following HPV vaccinations. In addition, increases in autoimmune diseases and any other diseases following HPV vaccinations have been denied, epidemiologically [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe plaintiff's legal team argued that, in theory, the HPV vaccinations could induce autoantibodies based on manuscripts by Darja Kanduc [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Kanduc compared the AA-sequences between all proteins of HPV16 (structural L1 and L2 and non-structural E1-E7 proteins) versus the human proteome. Kauduc claimed that large numbers of 7AA- or 8AA-length sequences, which were designated as \u0026ldquo;heptapeptide (or heptamer, 7-mer motif)\u0026rdquo; or \u0026ldquo;octapeptide,\u0026rdquo; respectively [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], and 5AA- or 6AA-length sequences (\u0026ldquo;pentapeptide, 5-mer motif\u0026rdquo; or \u0026ldquo;hexapeptide, 6-mer motif\u0026rdquo;) [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] were commonly present in HPV and human proteins. Kanduc\u0026rsquo;s data cannot be used as evidence that the HPV vaccine causes autoantibodies, since her manuscripts had the following scientific flaws. Although Kanduc compared AA-sequences of all HPV proteins with human proteins in her first report [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], the HPV vaccines contains only the HPV L1 protein, not the other HPV proteins (L2 and E1-E7). In addition, antibodies recognize and bind to specific AA sequences of the antigen, which is called an epitope. Although only the molecular mimicry between HPV L1 epitopes and host protein epitopes has the potential cross-reactive response, Kanduc compared the entire AA-sequences of HPV proteins and human proteomes, including non-epitope regions [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Later, Kanduc et al. compared a portion of the linear epitopes of HPV16 L1 protein (HPV16L1) with those of human proteins based on the erroneous hypothesis that if a partial sequence of the epitope matched a human protein, it could produce autoantibodies [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Immunologically, however, since an epitope is the smallest unit that reacts as an antigen to antibody binding, the discoveries of the similarities between parts of the epitope sequences and those of human epitopes, instead of the full-length sequence of epitopes, were irrelevant to cross-reactivities of anti-microbial antibodies to human proteins.\u003c/p\u003e\u003cp\u003eIn this study, we performed a computational analysis using the same methodology as Kanduc\u0026rsquo;s group. This study will help clarify the understanding of HPV vaccines by showing that the claim that HPV vaccines induce autoantibodies through molecular mimicry is incorrect.\u003c/p\u003e"},{"header":"2 Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Molecular mimicry analysis between the HPV16L1 and human epitopes\u003c/h2\u003e\u003cp\u003eUsing the method described by Kanduc et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], we identified the linear epitopes of the B cell receptor (antibody) against the HPV16 L1 in the Immune Epitope Database (IEDB) (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.iedb.org/\u003c/span\u003e\u003cspan address=\"https://www.iedb.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). In the IEDB, no L1 epitope of HPV type 18 was registered. Then, we compared the AA-sequences of HPV16 L1 epitopes of the human antibodies and the human protein epitopes of the human antibodies. The Basic Local Alignment Search Tool (BLAST) (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://blast.ncbi.nlm.nih.gov/Blast.cgi?PAGE=Proteins\u003c/span\u003e\u003cspan address=\"https://blast.ncbi.nlm.nih.gov/Blast.cgi?PAGE=Proteins\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) was used to determine whether the same AA-sequences in the HPV16 L1 epitopes could be found in human antibody epitopes of human proteins as described previously by Kanduc et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. We examined not only the AA-sequences of the full length of the linear epitopes, but also the portions of AA-sequences of the epitopes from five AA-length (pentapeptide) to 27 AA-length [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Molecular mimicry analysis using HBV and RSV\u003c/h2\u003e\u003cp\u003eWe identified the linear epitopes of the full-length hepatitis B virus (HBV) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and respiratory syncytial virus (RSV) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] on human B cell receptors in the IEDB. From the sequences of these HBV and RSV epitopes, we randomly generated five sets of the same numbers of AA-sequences as those generated from the HPV L1 epitopes: HBV sets 1\u0026ndash;3 and RSV sets 1 and 2 (\u003cb\u003eTables S1-5\u003c/b\u003e, note: in RSV set 2, we were not able to make the same numbers, but smaller numbers of 10-peptide, 11-peptide, 12-peptide and 13-peptide). Then, using the BLAST, we determined the numbers of AA-sequences among the HBV and RSV epitopes, which were identical to those of human B cell epitopes. HBV epitopes were from four open reading frames (ORFs): large hepatitis B surface antigen (PreS1, PreS2, and HBs); pre-core/core ORF (HBc and HBe); HBx (protein X); and DNA polymerase [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. RSV epitopes were from F protein, G protein, N protein, and P protein [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Molecular mimicry analysis using random AA-sequences and gene ontology analysis\u003c/h2\u003e\u003cp\u003eWe generated four sets of random AA-sequences (Random array sets 1\u0026ndash;4, \u003cb\u003eTables S6-9\u003c/b\u003e), which contained the same AA-length and sequence numbers as those of HPV16L1, using Excel's random number generator. We used the BLAST to identify the AA-sequences that matched human protein epitopes. We also conducted gene ontology analysis using the list of identified human proteins that shared the AA-sequences with AA-sequence of Random array sets, using the Gene Ontology Resource (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://geneontology.org/\u003c/span\u003e\u003cspan address=\"https://geneontology.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Statistical analysis\u003c/h2\u003e\u003cp\u003eWelch's \u003cem\u003et\u003c/em\u003e-test was used to compare the number of human proteins sharing the same AA-sequences with virus-derived and random sequences. Statistical analysis was performed using Prism 10.4 (GraphPad Software, Boston, MA).\u003c/p\u003e\u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.1 AA-sequence comparison between HPV and human epitopes\u003c/h2\u003e\u003cp\u003eTo analyze molecular mimicry between HPV L1 and human proteins, we used 22 linear epitopes of HPV16L1, whose AA-sequence lengths ranged from 9 to 27, registered in the IEDB; the AA-sequence lengths of the epitopes ranged from 9 to 27 (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). We found that no human proteins had identical sequences to the entire AA-sequences of the 22 linear epitopes. Thus, this computational analysis provided evidence that no antibodies against any epitopes of HPV16L1 would function as autoantibodies against human proteins.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eLinear epitopes of HPV16 L1 protein\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"13\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHPV epitope ID\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEpitope\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAA \u003c/p\u003e\u003cp\u003elength\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e9-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003e10-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003e11-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003e12-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003e13-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u003cp\u003eReferences and DOI\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e109332\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIHSMNSTIL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eZavaleta R et al. \u003cem\u003eJ Gen Virol\u003c/em\u003e 2004\u003c/p\u003e\u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1099/vir.0.80077-0\u003c/span\u003e\u003cspan address=\"10.1099/vir.0.80077-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e110602\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGLKAKPKFTLGKRKATPTT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" 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colname=\"c8\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eLenner P et al. \u003cem\u003eCancer Immunol\u003c/em\u003e 1995\u003c/p\u003e\u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/BF01517352\u003c/span\u003e\u003cspan address=\"10.1007/BF01517352\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e110652\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLCLIGCKPPIGEHWGKGSPC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" 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colname=\"c1\"\u003e\u003cp\u003e110825\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEDTYRFVTSQAIACQKHTPPA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eLeon S et al. \u003cem\u003eSex Transm Dis.\u003c/em\u003e 2009\u003c/p\u003e\u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/OLQ.0b013e318195762c\u003c/span\u003e\u003cspan address=\"10.1097/OLQ.0b013e318195762c\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e110863\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGLKAKPKFTLGKRKATPTTS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCason J et al. \u003cem\u003eInt J Cancer.\u003c/em\u003e 1992\u003c/p\u003e\u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ijc.2910500304\u003c/span\u003e\u003cspan address=\"10.1002/ijc.2910500304\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e110872\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGSGSTANLASSNYFP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e110898\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIACQKHTPPAPKEDPLKKYTFWEVNLK\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003eSharma BK et al. \u003cem\u003eEur J Cancer.\u003c/em\u003e 1996\u003c/p\u003e\u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/0959\u0026ndash;8049(96)00005\u0026ndash;6\u003c/span\u003e\u003cspan address=\"10.1016/0959\u0026ndash;8049(96)00005\u0026ndash;6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e110938\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLYIKGSGSTANLASSNYFPT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eLeon S et al. \u003cem\u003eSex Transm Dis.\u003c/em\u003e 2009\u003c/p\u003e\u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/OLQ.0b013e318195762c\u003c/span\u003e\u003cspan address=\"10.1097/OLQ.0b013e318195762c\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e110965\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePNNNKILVPKVSGLQYRVFR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e111088\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eACQKHTPPAPKEDDPLKKYT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\" morerows=\"6\" rowspan=\"7\"\u003e\u003cp\u003eDillner J et al. \u003cem\u003eInt J Cancer.\u003c/em\u003e 1990\u003c/p\u003e\u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ijc.2910450326\u003c/span\u003e\u003cspan address=\"10.1002/ijc.2910450326\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e111450\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eKGSPCTNVAVNPGDCPPLEL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e111581\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNGICWGNQLFVTVVDTTRST\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" 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colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e111585\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNKSEVPLDICTSICKYPDYI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e111890\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVDNRECISMDYKQTQLCLIG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e111915\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVHTGFGAMDFTTLQANKSEV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e175631\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePLGVGISGHPLLNKLDDTEN\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eYokomine M et al. \u003cem\u003eExp Ther Med.\u003c/em\u003e 2017\u003c/p\u003e\u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3892/etm.2017.4150\u003c/span\u003e\u003cspan address=\"10.3892/etm.2017.4150\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e175636\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePTPSGSMVTSDAQIFNKPYW\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e175665\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eVTSDAQIFNKPYWLQRAQGH\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e604717\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTSDAQIFNKP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003eTotal sequence number\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e327\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e305\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e283\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e261\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e239\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e217\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e196\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e176\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e156\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003eSubtracted total sequence number*\u003c/p\u003e\u003cp\u003e= Total sequence number \u0026ndash; overlapped sequence number\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e248\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e237\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e225\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e211\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e196\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e181\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e167\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e152\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e137\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"13\"\u003e*, Subtracted total sequence number (=\u0026thinsp;the precise total sequence number) was determined by subtracting the number of overlapped AA sequences among all AA sequences from the total sequence number. For example, the 3rd ID 110651 and the 4th ID 110652 were almost identical except for the 3rd ID had only one additional AA; 19 AA sequences were overlapped in two IDs. The 10-AA length epitope of the last ID 604717 was included in the two preceding ID 175636 and ID 175665. Subtracting these duplicate sequences yields the precise total number.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eNext, using the same approach as described by Kanduc [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], we examined the number of human proteins that share the portion of the AA-sequences of the HPV16L1 epitopes, although sharing the portion of AA-sequences of the HPV16L1 epitopes with human protein epitopes alone does not result in the production of cross-reactive autoantibodies. For example, when we analyzed an AA-sequence identity of one 9-mer HPV16L1 epitope, IHSMNSTIL (Epitope ID 109332, Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), to the human epitopes at the consecutive seven AA-sequence level, which was called \u0026ldquo;heptapeptide,\u0026rdquo; \u0026ldquo;heptamer,\u0026rdquo; or \u0026ldquo;7-mer motif\u0026rdquo; by Kanduc [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], one can identify three heptapeptides, each peptide of which was offset by one residue, overlapping by six residues: i.e., 1) IHSMNST, 2) HSMNSTI, and 3) SMNSTIL. Using all the AA-sequences of the 22 linear epitopes, consisting of 9\u0026ndash;27 AA-sequences, we were able to generate 248 pentapeptides (5AA-length). Then, using the BLAST search, we found that 1281 human protein epitopes shared at least one of these 248 pentapeptides (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Using the same method, we generated 237 hexapeptides (6AA-length) from the AA-sequences of the 22 epitopes; 106 human proteins shared at least one of these hexapeptides (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Similarly, 225 heptapeptides (7AA-length) were generated from the 22 epitopes shared with 16 human proteins; 211 octapeptides (8AA-length) shared with two human proteins; 196 nonapeptides (9AA-length) shared with two human proteins. No human protein had a sequence that was identical to the AA-sequence of HPV16L1 in 10AA or more than 10AA-length (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eNumber of human epitope AA sequences identical to viral epitope AA sequences\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"12\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" morerows=\"2\" nameend=\"c2\" namest=\"c1\" rowspan=\"3\"\u003e\u003cp\u003eVirus\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eViral protein\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"9\" nameend=\"c12\" namest=\"c4\"\u003e\u003cp\u003eAA length (number of AA sequences)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e8-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e9-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003e10-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003e11-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003e12-peptide\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003e13-peptide\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e(248)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e(237)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e(225)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e(211)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003e(196)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003e(181)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003e(167)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u003cp\u003e(152)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003e(137)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eHPV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHPV16 L1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1281\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e106\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"9\" rowspan=\"10\"\u003e\u003cp\u003eHBV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eSet 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLarge hepatitis B surface antigen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e1695\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e127\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ecore protein\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHBx\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eSet 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLarge hepatitis B surface antigen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e1549\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e104\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ecore protein\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHBx\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eSet 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eLarge hepatitis B surface antigen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e1667\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e167\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ecore protein\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHBx\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDNA polymerase\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e\u003cp\u003eRSV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eSet 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eG protein\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e1491\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e108\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN protein\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eF protein\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eSet2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eG protein\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e1720\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e117\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN protein\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eF protein\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP protein\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eRandom array\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSet 1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eNot applicable\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e825\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSet 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e972\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSet 3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e578\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSet 4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e649\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e3.2 HBV and RSV epitopes had larger numbers of AA-sequence homology with human epitopes than HPV epitopes\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThere were 249 linear epitopes registered in the IEDB that used the full-length HBV protein as an antigen. From these, we randomly selected epitopes consisting of 9\u0026ndash;27 AAs. From these epitopes, we generated the same number of AA-sequences as from the HPV16L1 epitopes, namely 248 pentapeptides (5AA-length); 237 hexapeptides (6AA-length); heptapeptides (7AA-length); 211 octapeptides (8AA-length); 196 nonapeptides (9AA-length); 181 10-peptides; 167 11-peptides; 176 12-peptides; and 138 13-peptides. Then, we generated three sets of these AA-sequence groups (HBV sets 1, 2, and 3) and examined the number of human proteins sharing these AA-sequences in HBV sets 1, 2, and 3 (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cb\u003eTables S1-3\u003c/b\u003e). Similarly, 159 linear epitopes were registered in the IEDB for the full-length human RSV protein. We followed the same approach for RSV as we did for HBV, creating two sets of groups of AA-sequences (RSV sets 1 and 2) and determining the number of human proteins that contained these AA-sequences (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cb\u003eTables S4-5\u003c/b\u003e). We compared the shared AA-sequence numbers at 5AA-, 6AA-, 7AA-, 8AA-, 9AA-, and 10AA-length levels. We found that the shared AA-sequence numbers in HPV epitopes were lower than those of HBV and RSV epitopes at all AA-length levels.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.3 Viral epitopes had more shared AA-sequences with human epitopes than random AA-sequences\u003c/h2\u003e\u003cp\u003eWe also randomly generated 9\u0026ndash;27 AA-length sequences, from which we generated four sets of 5\u0026ndash;13 AA-sequences (Random array sets 1, 2, 3, and 4) to determine the numbers of human epitope sequences identical to these random AA-sequences (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cb\u003eTables S6-9\u003c/b\u003e). When comparing the number of matching human epitopes for the three viral epitopes (HPV, HBV, and RSV combined) and for the Random array sets, the former were more common for penta-, hexa-, hepta-, octa- and nonapeptides (5 to 9 AA-length peptides). For example, at pentapeptide (5AA-length peptide) level, HPV had 1281; HBV sets 1\u0026ndash;3 had 1549 to 1695; RSV sets 1\u0026ndash;2 had 1491 to 1720; and Random array sets 1\u0026ndash;4 had 825 to 972 pentapeptides commonly found in human protein epitopes (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Statistically, the mean numbers of the common AA-sequences\u0026thinsp;\u0026plusmn;\u0026thinsp;standard error of the mean (SEM) were as follows (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e): 5AA-length, viral epitopes 1567.2\u0026thinsp;\u0026plusmn;\u0026thinsp;67.7, random array, 756.0\u0026thinsp;\u0026plusmn;\u0026thinsp;88.8, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 6AA-length, viral epitopes 121.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7, random array 44.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.9, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 7AA-length, viral epitopes 19.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9 random array 8.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01; 8AA-length, viral epitopes 7.7\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1, random array 3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.1; and 9AA-length, viral epitopes 4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1, random array 1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05. The numbers of matching human proteins for AAs derived from HPV16L1 epitopes were lower than for AAs derived from HBV and RSV epitopes. For example, the numbers of shared AA sequences at the 8AA level were as follows: HPV16L1, 2; HBV sets 1\u0026ndash;3, 5 to 16; RSV sets 1\u0026ndash;2, 6 and 12; and Random array sets 1\u0026ndash;4, 1 to 5. When the length of the AAs was ten or more (where the specificity was high), there was no difference between combined virus epitope sequences versus the Random array sets. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) (The mean common AA-sequence number\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM: 10AA-length, viral epitopes 1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63, random array 0.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.31).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eLastly, we conducted gene ontology analysis using human protein epitopes sharing 5 to 11 AA-sequences with HPV16L1, HBV (sets 1\u0026ndash;3), and RSV (sets 1\u0026ndash;2) epitopes, and four sets of random array sequences. We found that there was no statistically significant enriching gene ontology term in the human proteins sharing with any three viral epitope groups or Random array sets.\u003c/p\u003e\u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eTheoretically, when an in silico computational analysis shows that the full-length AA-sequences of the microbial epitopes are identical to a human protein epitope (i.e., having molecular mimicry), the microbial proteins have a potential to induce cross-reactive autoantibody production following microbial infections or vaccinations. On the other hand, when the analysis shows that only a portion of the epitope shared AA-sequences with host proteins, such \u0026ldquo;partial\" molecular mimicry alone likely does not result in the production of cross-reactive antibodies. In our study, using the same approach as Kanduc\u0026rsquo;s group [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], we examined the antibody epitopes of HPV16L1 and found that none of the entire AA-sequences of the 22 linear epitopes (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) were identical to any AA-sequences of human protein epitopes. Our result was consistent with findings by Kanduc\u0026rsquo;s group [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], who showed that there were no human protein epitopes identical to the HPV16L1 epitopes, although Kanduc\u0026rsquo;s group has never emphasized these crucial findings.\u003c/p\u003e\u003cp\u003eIn this study, we also showed the number of human proteins that had partial AA-sequence similarities to HPV16L1 epitopes. We found that HPV16L1 had fewer partial AA-sequence similarities than HBV and RSV epitopes. Although such \u0026ldquo;partial\u0026rdquo; molecular mimicry is irrelevant to the induction of cross-reactive autoantibodies, our results demonstrated that HPV16L1 epitopes were not unique in having a certain number of partial AA-sequence similarities with human protein epitopes, compared with other viral protein epitopes.\u003c/p\u003e\u003cp\u003eWe also demonstrated that viral protein epitopes (HPV16L1, HBV, and RSV) had more partial AA-sequence similarities with human protein epitopes than randomly generated AA sequences (i.e., Random array sets 1\u0026ndash;4) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Despite the evolutionary distance, humans and viruses may share specific sequence features that are biologically relevant for protein formation. On the other hand, for HPV16L1 epitope sequences, concordance with human proteins was equivalent to random sequences for AA-sequences of eight or more. Thus, human proteins did not have a highly specific match with the HPV16 L1 epitope sequences, although identical AA-sequences were commonly found at shorter AA-length levels (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eEpidemiologically, HPV vaccinations have been demonstrated not to increase the incidence of immune-mediated diseases or any diseases [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Experimentally, no researcher, including Kanduc's group, has ever demonstrated cross-reactivity between the HPV L1 protein and human tissues/proteins by enzyme-linked immunosorbent assay (ELISA) or other methods using anti-HPV sera, anti-HPV L1 antibodies, or autoantibodies [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Clinically, no studies have shown antibody deposition in the organs, increased autoantibody production, or efficacy of immunotherapies in alleged patients with HANS. It is now widely accepted in the scientific community that there is no point in suggesting the risk of autoimmune diseases by demonstrating the sharing of short peptide sequences by in silico analysis without supporting epidemiological data or experimental evidence [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eKanduc et al. performed computational analyses on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, using the same computational approach in their HPV vaccine studies, and reported that the SARS-CoV-2 vaccines could be dangerous due to the presence of 5\u0026ndash;7 AA-sequences shared between SARS-CoV-2 and human proteins [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Kanduc\u0026rsquo;s group also reported that vaccines against meningococcal B [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], diphtheria toxin [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], RSV [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], and HBV [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e] could pose risks due to the presence of 5\u0026ndash;7 shared AA-sequences with human proteins; some of the claims made by anti-vaccine advocates were based on these studies. None of these studies, however, experimentally tested whether vaccine-induced antibodies could cross-react with the plausible microbial epitopes or damage/kill the potential target human cell types/organs. As described above, the mere observation that certain AA-sequences of microorganisms have similarities to human proteins should not be used as a scientific basis for asserting vaccine risks.\u003c/p\u003e\u003cp\u003eAdverse events following vaccination should be carefully and scientifically evaluated. Lawsuits and claims of vaccine-associated adverse events based on a scientifically flawed hypothesis can leave suffering people with unresolved clinical signs/symptoms after HPV vaccinations and may pose a baseless health concern in the general public, reducing the vaccination coverage rate.\u003c/p\u003e\u003cp\u003eIn conclusion, we demonstrated that the identical AA-sequences to full-length HPV16L1 epitopes were not present among the human protein epitopes. We also demonstrated that HPV16L1 epitopes had fewer partial AA-sequence similarities than HBV and RSV epitopes. Therefore, it is incorrect to assert the risk of HPV vaccinations based on common AA-sequences in the HPV vaccines and human protein epitopes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank members of the Department of Obstetrics and Gynecology, Kindai University Faculty of Medicine, Fumitaka Sato and Sandesh Rimal of the Department of Microbiology, Kindai University Faculty of Medicine, and Ah-Mee Park of the Department of Arts and Sciences, Kindai University Faculty of Medicine.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupported by the Grant-in-Aid for Scientific Research KAKENHI from the Japan Society for the Promotion of Science (JSPS), JP23K08901 (R.S.), and JP22K18378/JP23K08901/JP24K10163 (I.T.), the Kindai University Research Enhancement Grant KD2506 (I.T.).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eN.M. received lecture fees from AstraZeneca, Takeda Pharmaceutical, MSD, and Eisai, and research grants from AstraZeneca and Eisai. N.M. is an outside director of Takara Bio Inc. Other authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eApproval of the research protocol by an Institutional Reviewer Board:\u0026nbsp;N/A\u003c/p\u003e\n\u003cp\u003eInformed Consent:\u0026nbsp;N/A\u003c/p\u003e\n\u003cp\u003eRegistry and the Registration No. of the study/trial:\u0026nbsp;N/A\u003c/p\u003e\n\u003cp\u003eAnimal Studies:\u0026nbsp;N/A\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eN.M. and I.T. conceived of and supervised the project. N.M. and K.N. designed the experiments. K.N. and N.M. conducted the experiments. K.N. and I.T. wrote the manuscript. K.S., R.S., and N.M. aided in the experiments and manuscript preparation. All authors have read and agreed to the published version of the manuscript. \u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eNakai H, Higashi T, Kakuwa T, Matsumura N (2024) Trends in gynecologic cancer in Japan: incidence from 1980 to 2019 and mortality from 1981 to 2021. Int J Clin Oncol 29(4):363\u0026ndash;371. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s10147-024-02473-8\u003c/span\u003e\u003cspan address=\"10.1007/s10147-024-02473-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKusakabe M, Taguchi A, Sone K, Mori M, Osuga Y (2023) Carcinogenesis and management of human papillomavirus-associated cervical cancer. 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Biologics 2010:4:75\u0026ndash;81. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2147/btt.s8890\u003c/span\u003e\u003cspan address=\"10.2147/btt.s8890\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Amino Acid Sequences, Autoimmunity, Cross Reactions, HANS, Uterine Cervical Neoplasms","lastPublishedDoi":"10.21203/rs.3.rs-7609715/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7609715/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAlthough human papillomavirus (HPV) vaccines are effective in preventing cervical cancer, the HPV vaccination rate in Japan is low due to concerns about alleged neurological adverse events, which were proposed in the ongoing HPV vaccine lawsuits. Based on the molecular mimicry theory by Darja Kanduc, plaintiffs' attorneys argued that HPV vaccines could cause organ damage due to cross-reactive autoantibodies. Kauduc proposed a flawed hypothesis that molecular mimicry would induce cross-reactive antibodies even when only the portions of amino acid (AA)-sequences of the epitopes were identical between microbial and human proteins.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e\u003cp\u003eIn this study, we conducted the same computational data analysis as Kanduc, using 22 linear epitopes (9\u0026ndash;23 AA-length) of the HPV type 16 L1 protein (HPV16L1) registered in the database.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe found that no human epitopes had identical AA-sequences to any HPV16L1 epitopes, demonstrating that HPV16L1 had no molecular mimicry with linear epitopes that have the potential to induce cross-reactive autoantibodies. On the other hand, we identified various numbers of human protein epitopes whose AA-sequences were partially identical with epitopes of HPV16L1, hepatitis B virus (HBV), and syncytial virus (RSV). We found that HPV16L1 had a smaller number of such proteins having \u0026ldquo;partial molecular mimicry\u0026rdquo; than HBV and RSV.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e\u003cp\u003eOur current \u003cem\u003ein silico\u003c/em\u003e analysis provided no evidence that HPV vaccinations could induce cross-reactive autoantibodies. The flawed molecular mimicry data should not be used as a scientific basis for alleged HPV vaccine-induced adverse events.\u003c/p\u003e","manuscriptTitle":"Lack of molecular mimicry between HPV vaccine L1 antigen and human proteins by a computational analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-29 17:35:50","doi":"10.21203/rs.3.rs-7609715/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-09-18T23:28:53+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-18T02:10:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-17T11:05:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Clinical Oncology","date":"2025-09-13T19:58:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"07ceae7a-2d6a-44f0-ba0f-9dd51c11e05a","owner":[],"postedDate":"September 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-12T16:05:41+00:00","versionOfRecord":{"articleIdentity":"rs-7609715","link":"https://doi.org/10.1007/s10147-026-02961-z","journal":{"identity":"international-journal-of-clinical-oncology","isVorOnly":false,"title":"International Journal of Clinical Oncology"},"publishedOn":"2026-01-08 15:58:51","publishedOnDateReadable":"January 8th, 2026"},"versionCreatedAt":"2025-09-29 17:35:50","video":"","vorDoi":"10.1007/s10147-026-02961-z","vorDoiUrl":"https://doi.org/10.1007/s10147-026-02961-z","workflowStages":[]},"version":"v1","identity":"rs-7609715","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7609715","identity":"rs-7609715","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}