Human Papillomavirus Detection by PCR Assay in a Large Series of High-Grade Squamous Intraepithelial Lesions with Cytohistological Correlation and Follow-Up

Abstract

Objective: High-grade squamous intraepithelial lesions (HSIL) are the precursors of invasive cervical carcinomas and are generally associated with the integration of mucosotropic human papillomavirus (HPV) DNA into the host cell genome. Detection of HPV is easy to perform nowadays, even in laboratories with limited technological capacity, and follow-up procedures for patients with HSIL are well established. Study Design: HPV detection was performed in a large group of patients with HSIL, and results were correlated with cytological, histological, and colposcopic findings. Discrepancies were examined and discussed. Results: Conventional Papanicolaou (Pap) screening detected 446 HSIL (0.20%) in 218,906 cervical smears. HPV detection by PCR was positive in 339/358 (94.7%) patients. The strains involved were: HPV 16 in 180 patients (53.1%), HPV 18 in 35 (10.3%), HPV 31/33 in 27 (8%), HPV 6/11 in 10 (2.96%), and an unidentified type in 73 (30%). For the last 97 patients (2006–2007), HPV typing was expanded with the following results: HPV 52 was detected in 9 patients (9.2%), HPV 58 in 6 (6.1%), HPV 51 in 4 (4.1%), HPV 68 in 2 (2.0%), and HPV 39 in 1 (1.0%). The number of nonidentified patients dropped to 9 (9.4%); in addition, 14/97 (14.4%) patients were infected with 2 or more viral types. Finally, 19 (5.3%) patients were HPV negative. Colposcopy revealed minor changes in 59 patients (17.3%), major changes in 264 (77.6%), and normal findings in 17 (5.1%). A biopsy was taken in 331/446 patients, and the diagnosis of HSIL or overt malignancy was histologically confirmed in 281 (84.9%) patients: CIN II in 46, CIN III in 224, and histologically upgraded in 11 (6 microinvasive squamous carcinomas, 1 squamous carcinoma, 2 in situ endocervical adenocarcinomas, and 2 microinvasive endocervical adenocarcinomas). Thirty-five patients (10.6%) were downgraded to CIN I and 15 (4.5%) patients had a negative biopsy. Follow-up in the negative-biopsy patients confirmed the existence of SIL in 11 patients [1 HSIL and 10 low-grade squamous intraepithelial lesions (LSIL)] while 4 were considered false positives (atrophic changes, 2; reactive changes, 2). After treatment, 31/331 (9.36%) patients displayed recurrence (HSIL in 29 and LSIL in 2). The viral strains involved in patients with recurrence were HPV 16 in 16 patients (51.6%); HPV 18 in 4 (12.9%); HPV 16 and 18 in 1 (3.2%); HPV 31 in 1 (3.2%); HPV 52 in 1 (3.2%); HPV 18, 31, and 58 in 1 (3.2%); HPV 68 in 1 (3.2%); HPV 51 and 73 in 1 (3.2%), and an unidentified type in 5 (16.1%). Follow-up in 14/19 HSIL and HPV-negative patients confirmed the existence of cervical pathology. Conclusions: HPV detection improves diagnostic sensitivity and provides an ideal tool for monitoring the response to treatment in HSIL patients. The pathogenic relevance of HPV strain 18 may be greater than previously assumed.

Assessment of Fine Needle Aspiration Specimen Adequacy for High-Risk HPV Detection and Genotyping in Oropharyngeal Squamous Cell Carcinoma

“…HPV genotyping has been used in gynecologic cytopathology in the past few years [4,5] but only recently is emerging as an important tool in the management of patients with OPC. Most publications in the literature are based on HPV 16 detection in surgical pathology specimens and use HPV detection methods such as PCR and ISH [6,7,8,9,10].…”

The association of pre-treatment HPV subtypes with recurrence of VIN

“…Evidence from cervical precancerous conditions suggested that HPV subtypes involved in pre-cancerogenic processes have an important role determining patients' prognosis [8,9]. Similarly, HPV persistence after treatment is the main prognostic factor influencing the risk of cervical dysplasia recurrence.…”

“…Evidence learned from cervical precancerous conditions suggests that different subtypes of HPV might correlate with different risk of persistence/recurrence and progression [8,9]. However, data regarding subtypes of HPV involved in VIN2+ and their significance are scant.…”