| Summary: | Background: Invasive cervical cancer (ICC) is the second most common cancer among women in developing countries where early age at first sexual intercourse (AFSI) and first pregnancy (AFP) are prevalent events. The epidemiological evidence of how these sexual and reproductive health (SRH) factors impact the natural history of human papillomavirus (HPV) and ICC remain inconclusive. It has been debated that a woman's risk for ICC will depend more on the "high-risk" sexual behaviour of the male partner than of her own behaviour. Passive smoking in the context of couples is unclear. The aim is to study SRH factors in relation to ICC risk in developing countries. Methods: Study 1 evaluated the risk of ICC and its association with AFSI and AFP in a pooled analysis of IARC case-control studies of ICC from eight developing countries. Study 2 assessed these SRH factors and risk of HPV persistence in a population-based natural history cohort study in Guanacaste, Costa Rica. Study 3 characterised the male role in the aetiology of ICC among couples in a pooled analysis of five ICC case-control studies and two cervical carcinoma in situ (CIS) case-control studies. Results: The ICC risk was 2.4-fold among those who reported AFSI and AFP :~a6 years compared with AFSI and AFP ~21 years. Decreasing AFP, not AFSI, was associated with an increased risk of a-year persistence. Lifetime number of sexual partners of the husband was the strongest predictor of CIS and ICC risk. The absence of circumcision was significantly associated with an increased risk of CIS. A 2-fold increased risk of ICC was also found among couples with both ever smoking men and women. These data confirm AFSI and AFP as risk factors for ICC, but any independent effects could not be distinguished. The association of AFP with HPV persistence suggests that AFP may play a more relevant role in cervical carcinogenesis. The combined effects of exposure to active and passive smoking suggest its potential adverse role in cervical carcinogenesis.
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