The 2S LGBTQIA+ (Two-Spirit, Lesbian, Gay, Bisexual, Trans, Queer and/or Questioning, Intersex, Asexual, and additional sexually and gender-diverse self-identities) population often faces barriers to care in the context of cervical cancer screening. With the shift from primary cervical cytology (Papanicolaou test) to primary human papillomavirus (HPV)-DNA testing, it is crucial to examine these populations’ healthcare needs. An intersectionality framework with an anti-oppressive lens is needed to restructure a healthcare system whose systems have traditionally erased the care needs of diverse populations through colonial, racialized, and cis-heteronormative practices. Barriers to cervical screening in 2S LGBTQIA+ populations include stigma, discrimination, limited provider guidance and understanding, and high rates of physical, sexual, and medical trauma. Self-sampling for HPV is a less invasive alternative to traditional Pap tests with a high rate of acceptability. The option to self-sample may increase participation in cervical screening based on improved privacy, comfort, and feelings of empowerment. Organizational, psychosocial, and physical recommendations for practice are shared to create a welcoming environment that reflects the diversity of populations in all aspects of healthcare. Affirmative care aims to make clients feel safe and accommodated by prioritizing dignity and respect as essential elements of eliminating cervical cancer in 2S LGBTQIA+ populations.