Low Rates of Dual-Site and Concordant Oral-Cervical Human Papillomavirus Infections and Cancers: A Systematic Review

HPV is the cause of almost all cervical cancer and is responsible for a substantial fraction of other anogenital cancers and oropharyngeal cancers. Understanding the HPV‐attributable cancer burden can boost programs of HPV vaccination and HPV‐based cervical screening. Attributable fractions (AFs) and the relative contributions of different HPV types were derived from published studies reporting on the prevalence of transforming HPV infection in cancer tissue. Maps of age‐standardized incidence rates of HPV‐attributable cancers by country from GLOBOCAN 2012 data are shown separately for the cervix, other anogenital tract and head and neck cancers. The relative contribution of HPV16/18 and HPV6/11/16/18/31/33/45/52/58 was also estimated. 4.5% of all cancers worldwide (630,000 new cancer cases per year) are attributable to HPV: 8.6% in women and 0.8% in men. AF in women ranges from 20% in India and sub‐Saharan Africa. Cervix accounts for 83% of HPV‐attributable cancer, two‐thirds of which occur in less developed countries. Other HPV‐attributable anogenital cancer includes 8,500 vulva; 12,000 vagina; 35,000 anus (half occurring in men) and 13,000 penis. In the head and neck, HPV‐attributable cancers represent 38,000 cases of which 21,000 are oropharyngeal cancers occurring in more developed countries. The relative contributions of HPV16/18 and HPV6/11/16/18/31/33/45/52/58 are 73% and 90%, respectively. Universal access to vaccination is the key to avoiding most cases of HPV‐attributable cancer. The preponderant burden of HPV16/18 and the possibility of cross‐protection emphasize the importance of the introduction of more affordable vaccines in less developed countries.

Several groups have outlined methodologies for systematic literature reviews of the effectiveness of interventions. The Effective Public Health Practice Project (EPHPP) began in 1998. Its mandate is to provide research evidence to guide and support the Ontario Ministry of Health in outlining minimum requirements for public health services in the province. Also, the project is expected to disseminate the results provincially, nationally, and internationally. Most of the reviews are relevant to public health nursing practice. This article describes four issues related to the systematic literature reviews of the effectiveness of public health nursing interventions: (1) the process of systematically reviewing the literature, (2) the development of a quality assessment instrument, (3) the results of the EPHPP to date, and (4) some results of the dissemination strategies used. The eight steps of the systematic review process including question formulation, searching and retrieving the literature, establishing relevance criteria, assessing studies for relevance, assessing relevant studies for methodological quality, data extraction and synthesis, writing the report, and dissemination are outlined. Also, the development and assessment of content and construct validity and intrarater reliability of the quality assessment questionnaire used in the process are described. More than 20 systematic reviews have been completed. Content validity was ascertained by the use of a number of experts to review the questionnaire during its development. Construct validity was demonstrated through comparisons with another highly rated instrument. Intrarater reliability was established using Cohen's Kappa. Dissemination strategies used appear to be effective in that professionals report being aware of the reviews and using them in program planning/policymaking decisions. The EPHPP has demonstrated the ability to adapt the most current methods of systematic literature reviews of effectiveness to questions related to public health nursing. Other positive outcomes from the process include the development of a critical mass of public health researchers and practitioners who can actively participate in the process, and the work on dissemination has been successful in attracting external funds. A program of research in this area is being developed.

Genital human papillomaviruses (HPVs) are commonly detected from clinical samples by consensus PCR methods. Two commonly used primer systems, the MY09-MY11 (MY09/11) primers and the GP5+-GP6+ (GP5+/6+) primers, amplify a broad spectrum of HPV genotypes, but with various levels of sensitivity among the HPV types. Analysis of the primer-target sequence homology for the MY09/11 primers showed an association between inefficient amplification of HPV types and the number and position of mismatches, despite accommodation of sequence variation by inclusion of degenerate base sites. The MY09/11 primers were redesigned to increase the sensitivity of amplification across the type spectrum by using the same primer binding regions in the L1 open reading frame. Sequence heterogeneity was accommodated by designing multiple primer sequences that were combined into an upstream pool of 5 oligonucleotides (PGMY11) and a downstream pool of 13 oligonucleotides (PGMY09), thereby avoiding use of degenerate bases that yield irreproducible primer syntheses. The performance of the PGMY09-PGMY11 (PGMY09/11) primer system relative to that of the standard MY09/11 system was evaluated with a set of 262 cervicovaginal lavage specimens. There was a 91.5% overall agreement between the two systems (kappa = 0.83; P < 0.001). The PGMY09/11 system appeared to be significantly more sensitive than the MY09/11 system, detecting an additional 20 HPV-positive specimens, for a prevalence of 62.8% versus a prevalence of 55.1% with the MY09/11 system (McNemar's chi(2) = 17.2; P < 0.001). The proportion of multiple infections detected increased with the PGMY09/11 system (40. 0 versus 33.8% of positive infections). HPV types 26, 35, 42, 45, 52, 54, 55, 59, 66, 73, and MM7 were detected at least 25% more often with the PGMY09/11 system. The PGMY09/11 primer system affords an increase in type-specific amplification sensitivity over that of the standard MY09/11 primer system. This new primer system will be useful in assessing the natural history of HPV infections, particularly when the analysis requires HPV typing.