We performed a multicentric, retrospective cohort study that involved two Italian centers: IRCCS Fondazione Policlinico San Matteo, Pavia, and Luigi Sacco Hospital, ASST-Fatebenefratelli-Sacco, University of Milan, Milan. All WLWH who attended the colposcopic services of the two institutions from 1999 to 2019 were retrospectively identified by searching the clinical databases.
Those patients who presented at entry with a normal Pap smear and a negative HR-HPV test and who had at least one year of follow-up were selected for the analysis. Exclusion criteria were: age 21 years or older, ongoing pregnancy, treatment for CIN or total hysterectomy before enrollment. Institutional Review Board (IRB) approval by our institution was obtained (RC805036 IRCCS Fondazione Policlinico San Matteo, Pavia, Italy).
Anamnestic items about sociodemographic and clinical features were compiled after structured interviews during enrollment and the follow-up. All patients were evaluated every 6–12 months according to an established protocol, including a Pap smear, HPV test, and colposcopy with targeted biopsies if necessary. Abnormalities in cervical cytology were classified according to the most recent Bethesda system terminology [14 (link)]. Cytology examinations performed before the introduction of the Bethesda system terminology were revised by the pathologists of each institution involved in the study. The colposcopic examinations were recorded, taking into consideration the 2011 revised colposcopic terminology of the International Federation for Cervical Pathology and Colposcopy (IFCPC) [15 (link)]. Cervical samples for the HPV test were obtained immediately before colposcopy, and scrapes were taken with a cervix brush, suspended in Thin Prep Preserve Cyt Solution (Cytic Corporation, Marlborough, MA, USA), and stored at 4 C. HPV type-specific sequences were detected by the line probe assay INNO-LiPA HPV genotyping assay version V2 up to 2009 and version EXTRA subsequently (Fujirebio Europe, Gent, Belgium), according to the manufacturer’s instructions. The International Agency for Research on Cancer (IARC) classified HPV types into the following categories: high-risk HPV with proven carcinogenicity (16, 18, 31, 33, 45, 52, 58, 26, 35, 39, 51, 53, 56, 59, 66, 68, 73, 82) and low-risk HPVs (6, 11, 40, 43, 44, 54, 69, 70, 74) [16 (link)]. We considered persistent infection the detection of HPV DNA for at least 2 years.
The colposcopic examination was performed by two experienced gynecologists (BG and AA) certified by the Italian Society of Colposcopy and Cervico-Vaginal Pathology (SICPCV). Targeted cervical biopsies were obtained in all cases where a cervical lesion was suspected and in all cases of high-grade squamous cervical lesions (HSIL), irrespective of the colposcopic impression. Endocervical curettage was performed, according to the clinician’s judgment, when the extent of the lesion or the squamocolumnar junction was not entirely visible (transformation zone type 3). Histopathologic results were reported according to Lower Anogenital Squamous Terminology (LAST) as LSIL (CIN1), HSIL (CIN2), HSIL (CIN3), or HSIL (CIN2/3) [17 (link)]. The use and type of antiretroviral therapy were recorded on the basis of the medications listed in the patients’ charts. HAART was defined as the co-administration of two nucleoside reverse-transcriptase inhibitors and at least one of the following: a protease inhibitor, a non-nucleoside reverse-transcriptase inhibitor, or an additional nucleoside reverse-transcriptase inhibitor. All other types of ART (mono- or dual-nucleoside reverse-transcriptase inhibitors) were defined as pre-HAART. CD4+ T-lymphocyte count was considered according to the Centers for Disease Control’s revised surveillance case definition for HIV infection [18 ]. The classes of HIV-related immunodeficiency were reported in accordance with the WHO immunologic classification for established HIV infection [19 ]. These classifications identify the following classes: none or not significant for a CD4+ T-cell count of 500 cells/µL; mild for a CD4+ T-cell count of 350–499 cells/µL; advanced for a CD4+ T-cell count of 200–349 cells/µL; and severe for a CD4+ T-cell count of 200 cells/µL.
Those patients who presented at entry with a normal Pap smear and a negative HR-HPV test and who had at least one year of follow-up were selected for the analysis. Exclusion criteria were: age 21 years or older, ongoing pregnancy, treatment for CIN or total hysterectomy before enrollment. Institutional Review Board (IRB) approval by our institution was obtained (RC805036 IRCCS Fondazione Policlinico San Matteo, Pavia, Italy).
Anamnestic items about sociodemographic and clinical features were compiled after structured interviews during enrollment and the follow-up. All patients were evaluated every 6–12 months according to an established protocol, including a Pap smear, HPV test, and colposcopy with targeted biopsies if necessary. Abnormalities in cervical cytology were classified according to the most recent Bethesda system terminology [14 (link)]. Cytology examinations performed before the introduction of the Bethesda system terminology were revised by the pathologists of each institution involved in the study. The colposcopic examinations were recorded, taking into consideration the 2011 revised colposcopic terminology of the International Federation for Cervical Pathology and Colposcopy (IFCPC) [15 (link)]. Cervical samples for the HPV test were obtained immediately before colposcopy, and scrapes were taken with a cervix brush, suspended in Thin Prep Preserve Cyt Solution (Cytic Corporation, Marlborough, MA, USA), and stored at 4 C. HPV type-specific sequences were detected by the line probe assay INNO-LiPA HPV genotyping assay version V2 up to 2009 and version EXTRA subsequently (Fujirebio Europe, Gent, Belgium), according to the manufacturer’s instructions. The International Agency for Research on Cancer (IARC) classified HPV types into the following categories: high-risk HPV with proven carcinogenicity (16, 18, 31, 33, 45, 52, 58, 26, 35, 39, 51, 53, 56, 59, 66, 68, 73, 82) and low-risk HPVs (6, 11, 40, 43, 44, 54, 69, 70, 74) [16 (link)]. We considered persistent infection the detection of HPV DNA for at least 2 years.
The colposcopic examination was performed by two experienced gynecologists (BG and AA) certified by the Italian Society of Colposcopy and Cervico-Vaginal Pathology (SICPCV). Targeted cervical biopsies were obtained in all cases where a cervical lesion was suspected and in all cases of high-grade squamous cervical lesions (HSIL), irrespective of the colposcopic impression. Endocervical curettage was performed, according to the clinician’s judgment, when the extent of the lesion or the squamocolumnar junction was not entirely visible (transformation zone type 3). Histopathologic results were reported according to Lower Anogenital Squamous Terminology (LAST) as LSIL (CIN1), HSIL (CIN2), HSIL (CIN3), or HSIL (CIN2/3) [17 (link)]. The use and type of antiretroviral therapy were recorded on the basis of the medications listed in the patients’ charts. HAART was defined as the co-administration of two nucleoside reverse-transcriptase inhibitors and at least one of the following: a protease inhibitor, a non-nucleoside reverse-transcriptase inhibitor, or an additional nucleoside reverse-transcriptase inhibitor. All other types of ART (mono- or dual-nucleoside reverse-transcriptase inhibitors) were defined as pre-HAART. CD4+ T-lymphocyte count was considered according to the Centers for Disease Control’s revised surveillance case definition for HIV infection [18 ]. The classes of HIV-related immunodeficiency were reported in accordance with the WHO immunologic classification for established HIV infection [19 ]. These classifications identify the following classes: none or not significant for a CD4+ T-cell count of 500 cells/µL; mild for a CD4+ T-cell count of 350–499 cells/µL; advanced for a CD4+ T-cell count of 200–349 cells/µL; and severe for a CD4+ T-cell count of 200 cells/µL.
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