HPV has long been constructed as a sex-specific virus. Boys and men largely perceive the virus as not related to themselves and thus develop a female-specific schema on HPV. The present study investigates message strategies for promoting HPV vaccination among heterosexual young men in the United States. Through an online experiment, this study examined the effects of reference point (self, other, vs. self-other) and message framing (gain vs. loss) on processing fluency, optimistic bias, and behavioral intentions. The findings showed a schema-matching pattern in facilitating information processing, and a schema-mismatching pattern in attenuating optimistic bias. Specifically, other-referencing messages that related the outcomes of getting vaccinated for HPV to the message recipients' sexual partners promoted processing fluency and widened the self-other gap in perceived susceptibility to HPV, regardless of the message frame. By contrast, self-other-referencing messages that highlighted the outcomes regarding themselves and their sex partners enhanced processing fluency and mitigated optimistic bias. Moreover, the attenuation in optimistic bias increased the participants' information seeking intentions and the likelihood that they would share the messages on social media. The implications for health message design are discussed from a schema-based, message-tailoring perspective.