There is a consensus that a persisting infection with human papillomavirus (HPV) is the main causative agent for the development of a cervical carcinoma. Testing for HPV therefore plays an important role in cervical cancer screening. Suggestions have been made to introduce the HPV test as the primary screening method, replacing cytology as the current screening technique. However, there is discussion on the value of HPV-negative high-grade cytological lesions.
It is of vital importance to establish whether using an HPV test as the primary screening method for cervical cancer will result in missing high-grade cytological lesions, which are the precursors of cervical carcinomas. This systematic review gives an overview of the percentage of women with high-grade lesions on cytology (ASC-H and HSIL) and a negative HPV test, who present with moderate or severe dysplasia or with a malignancy on histology.
A comprehensive literature search was carried out, including MEDLINE (PubMed, 1 January 2001 until 25 November 2016) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library). 925 titles and abstracts were screened. 40 eligible studies included women presenting with a cervical cytology result of ASC-H or HSIL and an HPV-negative test result, who were subsequently subjected to reference standard verification with colposcopy and colposcopy directed biopsies for histologic verification. Two review authors independently extracted data from the selected articles and assessed the quality of the studies. Disagreements were resolved by consensus.
The percentage of females who develop moderate to severe dysplasia or a malignancy (CIN2+) from HPV-negative ASC-H is 10,7%, 95%CI [5,3; 16,0]. The percentage CIN2+, originated from HPV-negative HSILs, is 35,9%, 95%CI [28,4; 43,4].
Histologically confirmed CIN2+ lesions out of an HPV-negative high-grade cytological population are an existing, yet insufficiently studied entity. Consequently, it might result in missing high-grade precursor lesions when HPV testing would be used as a unique primary screening test for cervical cancer. Additional research is needed to establish the prevalence and the importance of HPV-negative high-grade cytological lesions in Belgium in order to determine the most appropriate screening method.