Table 1.
Findings of Studies That Evaluated Interactions Between Different Types of Human Papillomavirus in the Context of Multiple-Type Infections in the Past 5 Years
| First Author, Year (Reference No.) | Study Population | Study Location | Study Sample | HPV Vaccination Status | Age, years | HPV Detection Method | No. of HPV Types Detected | Results/Conclusions |
|---|---|---|---|---|---|---|---|---|
| Wentzensen, 2014 (32) | Population-based study | New Mexico, United States | 59,664 women | Unvaccinated | ≤30 vs. >30 | LINEAR ARRAY HPV Genotyping Test (Roche Diagnostics, Indianapolis, Indiana) | 37 | Observed additive effects of HPV types on risk of high-grade squamous intraepithelial lesions in multiply infected women |
| Mollers, 2014 (33) | Self-collected vaginal samples from 3 cross-sectional studies; high-risk setting | The Netherlands | 3,874 women | Unvaccinated | 16–29 | SPF10-DEIA/HPVLiPA25, version 1 (Labo Bio-Medical Products B.V., Rijswijk, the Netherlands) | 25 | No evidence for particular type-type interaction found; findings suggested that clustering differs among HPV types and varies across risk groups |
| Querec, 2013 (34) | Immune-competent women, self- and clinician-collected cervicovaginal samples; mostly routine screening population | Pooled data from 6 different studies, United States | 32,245 women | Unvaccinated | 11–83 | LINEAR ARRAY HPV Genotyping Test | 37 | Infections with multiple HPV types were detected more often than expected; negative associations were few and less significant, supporting the expectation of no type replacement with vaccination |
| Rositch, 2012 (35) | HIV-negative uncircumcised men | Kenya | 1,097 men | Unvaccinated | 18–24 | GP5+/GP6+ primers and EIA | 44 | No evidence of potential for type replacement and competition |
| Campos, 2011 (15) | Guanacaste HPV Natural History Study | Costa Rica | 980 women, 1,646 infections | Unvaccinated | 18–>47 | MY09/MY11 polymerase chain reaction | >40 | Concurrent, prevalent detection of additional HPV types did not change the likelihood of viral persistence |
| Chaturvedi, 2011 (13) | Costa Rica HPV16/18 Vaccine Trial | Costa Rica | 5,871 women | Unvaccinated | 18–25 | SPF10-DEIA/HPVLiPA25 | 25 | Coinfecting HPV genotypes occur at random and lead to cervical disease independently |
| Carozzi, 2012 (36) | NTCC cohort | Multiple countries in Europe | 36,778 women | Unvaccinated | 25–60 | GP5+/GP6+ primers and RLB | 13 | 24% of Hybrid Capture 2–positive women (Digene Corporation, Gaithersburg, Maryland) were multiply infected; coinfections occurred more frequently than expected by chance |
| Vaccarella, 2011 (37) | Guanacaste HPV Natural History Study | Costa Rica | 8,424 women | Unvaccinated | 18–84; mean ≈ 40 | MY09/MY11 primers | >40 | Prevalence of multiple infection was 7.3% overall and 33% among HPV-positive women; coinfection occurred more often than expected by chance; degree of clustering increased with genetic similarity of L1 region |
| Vaccarella, 2010 (23) | IARC HPV prevalence surveys (15 studies) | Multiple countries, worldwide | 14,176 women | Unvaccinated | ≥15; mean ≈ 41 | GP5+/GP6+ primers; typing by either RLB or EIA | 36 | Prevalence of coinfection was 3% overall and 26% among HPV-positive women (15 types); some of the observed excess differed by genotyping method (only in EIA, not in RLB) |
| Palmroth, 2012 (14) | HPV vaccine trial participants | Finland | 4,808 (approximately 2,400 HPV-vaccinated and, in the control arm, HAV-vaccinated) women | Vaccinated and unvaccinated | 16–17 | SPF10-DEIA/HPVLiPA25 | 25 | No excess risk of either low-risk or high-risk HPVs in vaccinated women; in the control (HAV) arm, HPV 18-positive women had increased likelihood of α7 types |
| Wentzensen, 2009 (16) | Women referred to colposcopy for abnormal cytology | Oklahoma, United States | 1,670 women | Unvaccinated | 18–81; median, approximately 25 | LINEAR ARRAY HPV Genotyping Test | 37 | Younger women were more likely to have multiple infections; results did not show synergistic or antagonistic clustering of genotypes |
Abbreviations: EIA, enzyme immunoassay; HAV, hepatitis A virus; HIV, human immunodeficiency virus; HPV, human papillomavirus; IARC, International Agency for Research on Cancer; NTCC, New Technologies in Cervical Cancer; RLB, reverse line blot.