**5. Summary**

In summary, the relevance of HPV infections requires a close monitoring, especially in certain groups o individuals (e. i. Women older than 30 years old). The accuracy of methos using NAATs has emerged as election in the control of HPV infection. But the search is ongoing for safer: more precise markers which may allow for a better control of the infection [134]. These markers include genome quantification via real-time PCR, viral integration into the human genome via E2-E1/E6-E7 genes ratio or the search of viral variants by sequencing, pyrose‐ quencing or allelic discrimination techniques [24, 109, 135].

Addition of new technologies into existing, highly efective screening programs are considered according to the ability to increase the efficiency of the program (high sensitivity with reduction in unnecessary follow-up of minor, transient infection) [136].

**Technology Benefits Limitations**

Single analyte (p16protein) to detect infection

May increase specificity by detecting active

As a marker of disease and not infection, may

Objective output. High cost

Subjective output High cost

Subjective output Questionable reproducibility

with any high-risk HPV

infection

increase specificity

increase specificity

increase specificity

**TERC-gain** As a marker of disease and not infection, may

May be useful as a pronostic marker

**TERC:** telomerase RNA component. Adapted from Gravitt et al [135]

**Table 2.** Screening and progression prognostic biomarkers technologies.

As a marker of disease and not infection, may

Potential to increase specificity Moderate complexity for DNA methods

Objective output. Very high complexity to detect integrated

Subjective output Not compatible with all collection buffers Cost may be lower than DNA/RNA test Order of sampling may affect performance

Compatible with urine sampling Sensitivity limited; questionable reproducibility

transcripts

High cost

Low specifity

High complexity

Very high complexity

High complexity

High cost

Requires type-specific assay

Moderate complexity

Integrated DNA may not be transcriptionally active

Molecular Diagnosis of Human Papillomavirus Infections

http://dx.doi.org/10.5772/55706

15

Common occurrence of mixed episomal and integrated HPV in cervical intraepithelial neoplasia

Compatibility with self-sampling unknown

**HPV integration**

**p16 enzyme liked**

**inmunobsorbe nt assay**

**Methylacion profile**

**Other proliferation/ cell cycle markers**

The table 2 presents a summary of the technologies relative to their intended or perceived benefit and limitations compared to existing screening and progression prognostic biomarkers methods [136].



**Table 2.** Screening and progression prognostic biomarkers technologies.

Addition of new technologies into existing, highly efective screening programs are considered according to the ability to increase the efficiency of the program (high sensitivity with

14 Human Papillomavirus and Related Diseases – From Bench to Bedside A Diagnostic and Preventive Perspective

The table 2 presents a summary of the technologies relative to their intended or perceived benefit and limitations compared to existing screening and progression prognostic biomarkers

**HCII** Non radioactive signal amplification method Not identification of specific HPV genotypes

Useful for test of cure. Algorithms may be too complicated to be readily

Objective output. RNA less stable, not compatible with some

Objective and quantitative output. Not pronostic (except for HPV 16)

Cross-reactivity between high-risk and low-risk HPV

Moderate to high complexity even with standardized commercial reagents.

translated into clinical practice.

common collection buffers

High cost

High cost

Compatibility with self-sampling unknown

Requires type-specific quantitation

Very difficult to establish consensus primer-based genotyping de novo with adequate quality control

reduction in unnecessary follow-up of minor, transient infection) [136].

**Technology Benefits Limitations**

Distinguishes between the high-risk and low-risk

Similar analytic sensitivity to some PCR methods

**PCR** Non radioactive signal amplification method Contamination

Discrimination of HPV-18/18 from other high-risk types may have greater positive predictive value.

Amenable to use with self-sampling. High cost

**HPV mRNA** Potential to increase specificity Moderate to high complexity

**HPV viral load** Potential to increase specificity High complexity

May differentiate sequential infection with different types from persistent infection with the

Compatible with many collection buffers.

Amenable to use with many-samples

methods [136].

**HPV genotyping** HPV

Low cost

same type.

Objective output.

for HPV DNA detection
