The increasing uptake of HPV vaccination and incorporation of HPV primary screening/partial genotyping with reflex cytology for non 16/18 positive women has, and will continue to lower the prevalence of high grade disease and impact the operating characteristics of cytology as a screening test.  Since the specificity of HPV testing for high-grade CIN is low, methods are needed for selecting which HPV positive women need colposcopy. Both the cross-sectional and the longitudinal accuracy of a candidate marker for triage are relevant, the latter in order to define at which interval women need retesting.  So how can we maintain quality, both sensitivity and specificity for cytology testing?

(1) Morphology: The primary goal of the cervical cytology Bethesda 2014 update and third edition of the atlas was to share additional morphologic features, pitfalls and clues to improve locator and interpretive skills for the detection of high grade disease. Implementation of the LAST/WHO two tier LSIL/HSIL terminology for reporting histopathology of HPV associated squamous lesions of the anogenital tract, along with appropriate triage with biomarker p16 has also improved the reproducibility of histology and cytologic-histologic correlation in cervical cancer screening.

(2) Informed cytology. Cytology triage is attractive in the sense that it takes advantage of the high sensitivity of HPV testing as the primary screen while relying on the high specificity of cytology to triage those women found to be positive on first screen. However, data has accumulated to suggest that cytology interpreted with knowledge of the HPV status (informed cytology) is more sensitive than cytology read without knowledge of the HPV as well as data showing that there is a bias to overcall cytology and decrease the accuracy of the Pap test in the setting of a known concurrent positive HPV.

 (3) Molecular methods. When considering implementation of any screening test an optimal balance of sensitivity and specificity needs to be emphasized to balance the harms and benefits of screening. After the incorporation of high risk HPV DNA and mRNA testing in the clinical realm of cervical cancer screening, evaluation of other molecular markers for triage and prognostication is ongoing. Recent studies have shown that p16/Ki-67 dual immunostaining of cytology specimens increases the detection of CIN2+ compared with cytologic review and this approach has been proposed for implementation into clinical practice. The multistep nature of carcinogenesis contains sequential accumulations of genetic changes that lead to progression and invasive growth. Hypermethylation, genomic mutations and miRNA have been shown to be associated with progression of cervical precancer and invasion.

(4) Automation: Use of computer assisted screening devices, with potentially superior sensitivity for rare event detection may play an increasing role in morphology-based screening and triage to maintain the level of sensitivity needed to continue effective manual-based morphologic screening.

(5) Cytology Workforce- Maintaining a high quality cytology screening operation, requires a skilled cytotechnologist workforce. Recruitment and retention of cytotechnologists has become a major issue since the decrease in cytology volumes due to use of hrHPV testing and increasing intervals.

(6) Telemedicine and Other global initiatives: Teleconsultation has shown promise in supporting areas without access to cytopathology expertise. Professional organizations and volunteers have made an impact in setting up and training individuals in developing countries where HPV testing has not been implemented. Cytology will remain a part of cervical cancer prevention for sometime to come, hence maintain its quality is an important consideration.