Table 2.

Studies addressing the impact of HPV infection on pregnancy outcome.

Authors, Year	Study Type	Sample	HPV Detection	HPV Type	HPV History (e.g., Previous History of CIN, Genital Warts)	Conclusions
Cotton-Caballero et al., 2017 [91,92]	Retrospective cohort study (2153 pregnant women)	Cervical samples	Cervical cytology HPV genotyping	HR-HPV (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68)	Patients with treated cervical dysplasia (conization, loop electrosurgical excision procedure, and cryotherapy) were included and adjusted for	HR-HPV infection led to an increase in PPROM and preterm birth resulting from PPROM, but not preterm birth without PPROM
Huang et al., 2014 [93]	Systematic review (8 studies)	Cervical samples	Cervical cytology HPV DNA testing (ISH, PCR)	HR-HPV LR-HPV undefined	Two studies in the meta-analysis included adjustment for prior cervical procedures	HR-HPV-infected women had an overall 2.55-fold increased risk of delivering prematurely
Zuo et al., 2011 [94]	Retrospective study (2480 cases)	Cervical samples Placental tissue	Cervical cytology Reflex HPV DNA testing via RNA-DNA hybrids Pathologic examination of the placenta	HR-HPV	Not specified	HR-HPV-related changes in cervical cytology were associated with preterm birth and placental abnormalities
Gomez et al., 2008 [62]	Case–control study (108 cases)	Placental tissue	HPV DNA testing (PCR) followed by HPV type confirmation via DNA sequencing	HR-HPV (types 16, 18) LR-HPV (types 6, 11)	Not specified	HR-HPV infection was correlated with placental abnormalities and preterm delivery HR-HPV infection did not increase the risk of preeclampsia
Niyibizi et al., 2021 [95]	Prospective cohort study (899 pregnant women)	Vaginal secretion samples Placental tissue	HPV DNA testing and genotyping (PCR)	HR-HPV LR-HPV	7.1% of women had previously undergone treatment for CIN	Persistent vaginal HPV-16/18 infection and placental HPV infection were associated with an increased risk of preterm delivery Treatment for HR-HPV-related cervical dysplasia also increased the risk of delivering prematurely
Wiik et al., 2021 [96]	Retrospective population-based register study (400,583 pregnant women)	Cervical samples	HPV DNA testing Cervical cytology Cervical histology	Not specified	Women previously treated for CIN were excluded from this study	HPV infection identified via DNA testing was associated with a higher risk of PPROM than HPV infection, certified through cytology, without DNA testing Both positive cytology and positive HPV DNA testing were associated with an increased risk of preterm delivery, PROM, PPROM, and neonatal mortality
Aldhous et al., 2019 [85]	Data-linkage study (5598 pregnant women)	Cervical samples	HPV DNA testing Cervical cytology Cervical histology	HR-HPV LR-HPV undefined	No data regarding previous treatments for HPV-associated cervical disease	High-grade HPV-related cervical disease was associated with an increased risk of preterm birt hLow-grade HPV-related cervical disease and HR-HPV infection with no disease did not increase the risk of preterm delivery
Ambühl et al., 2017 [97]	Prospective case–control study (271 pregnant women)	Placental tissue	HPV DNA detection via nested PCR, followed by HPV genotyping via CISH	HR-HPV LR-HPV	Patients with genital warts, cervical dysplasia/carcinoma in situ/cancer were included in this study	Placental HPV infection was more frequent among women with history of cervical cancer The prevalence of placental HPV was similar in both complicated and uncomplicated pregnancies
Subramaniam et al., 2016 [84]	Retrospective cohort study (2321 pregnant women)	Cervical samples	HPV DNA testing Cervical cytology	HR-HPV	Women previously treated for CIN were excluded from this study	HR-HPV infection did not increase the risk of developing pregnancy-induced hypertensive disorders (PIHDs) and/or delivering prematurely HR-HPV infection was associated with an increased risk of placental abruption and severe preeclampsia
Ambühl et al., 2016 [98]	Systematic literature search (42 studies)	Cervical samples Placental tissue	HPV DNA testing (PCR, DNA chip, hybrid capture, Southern blot) Pathologic examination of the placenta	HR-HPV LR-HPV	Studies either included or excluded women with HPV-related lesions One-third of studies did not specify this aspect	Overall, the authors concluded that HPV infection could increase the risk of spontaneous abortion or spontaneous preterm delivery
Conde-Ferráez et al., 2013 [83]	Case–control study (127 cases)	Cervical samples	HPV DNA testing (PCR) HPV genotyping (NMPCR)	HR-HPV LR-HPV	Not specified	No significant association between HPV infection and spontaneous abortion was found
Cho et al., [87]	Cross-sectional study (311 cases)	Cervical samples	HPV DNA testing (via RNA–DNA hybrids)	HR-HPV	Not specified	HR-HPV infection was associated with an increased risk of PROM at term HR-HPV infection was not linked to a higher risk of preeclampsia
Nimrodi et al., 2018 [99]	Retrospective cohort study (15,357 cases)	Cervical samples	Cervical cytology	Not specified	Not specified	HPV infection did not increase the risk of developing preeclampsia, cervical insufficiency, placental abruption, PROM, PPROM, or preterm delivery
McDonnold et al., 2013 [100]	Retrospective cohort study (942 cases)	Cervical samples	Cervical cytology HPV DNA testing	HR-HPV	Not specified	HR-HPV appeared to contribute an approximately two-fold increase in preeclampsia risk
Slatter et al., 2015 [65]	Cross-sectional study (339 cases)	Placental tissue	Pathologic examination of the placenta	HPV DNA testing (IHC, CISH, PCR)	History of cervical HPV infection was available for two=thirds of women	Placental HPV infection was linked to negative pregnancy outcomes and complications, such as preterm birth, fetal growth restriction, fetal demise, diabetes, and preeclampsia Previous cervical HPV infection was a risk factor for developing placental HPV infection
Ford et al., 2019 [89]	Data-linkage study (31,827 pregnant women)	Cervical samples	Cervical cytology	Not specified	Women with previous abnormal cervical cytology were included in the study and adjusted for	Abnormal Pap results were an independent risk factor for IUGR, and especially very low birthweight
Giambanco et al., 2020 [101]	Case series (20 cases)	Cervical samples	Cervical cytology HPV DNA testing (multiplex RT-PCR)	HR-HPV LR-HPV (but not specified)	Women with previous history of CIN and/or abnormal Pap smears were excluded from the study	HPV infection was not associated with adverse pregnancy outcomes such as miscarriage, PPROM, and preterm birth

CIN—cervical intra-epithelial neoplasia; PCR—polymerase chain reaction; RT-PCR—real-time polymerase chain reaction; NMPCR—nested multiplex polymerase chain reaction; ISH—in situ hybridization; CISH—chromogenic in situ hybridization; IHC—immunohistochemistry.